Variant summary: The DHCR7 c.1341C>T (p.Asp447Asp) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may eliminate ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 399/117638 control chromosomes (6 homozygotes) at a frequency of 0.0033918, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301).Review publications, Jira_2003 and Wareham_2000, classify the variant as a "polymorphism," along with a publication indicating the variant to have been found in a cohort of SLOS patients and classified it as "polymorphism," as well as suggesting the variant may have co-occurred with a deleterious DHCR7 variant. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." Taken together, this variant is classified as "likely benign."
ClinVar Genomic variation as it relates to human health
NM_001360.3(DHCR7):c.1341C>T (p.Asp447=)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(15)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign/Likely benign
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001360.3(DHCR7):c.1341C>T (p.Asp447=)
Variation ID: 93709 Accession: VCV000093709.60
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.4 11: 71435462 (GRCh38) [ NCBI UCSC ] 11: 71146508 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 2, 2016 Oct 20, 2024 Jul 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001360.3:c.1341C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001351.2:p.Asp447= synonymous NM_001163817.2:c.1341C>T NP_001157289.1:p.Asp447= synonymous NC_000011.10:g.71435462G>A NC_000011.9:g.71146508G>A NG_012655.2:g.17970C>T LRG_340:g.17970C>T LRG_340t1:c.1341C>T LRG_340p1:p.Asp447= - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000011.10:71435461:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00280 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00280
1000 Genomes Project 30x 0.00281
The Genome Aggregation Database (gnomAD) 0.00296
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00354
Trans-Omics for Precision Medicine (TOPMed) 0.00357
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| DHCR7 | - | - |
GRCh38 GRCh37 |
937 | 952 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 29, 2019 | RCV000079642.25 | |
| Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2024 | RCV000512660.41 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001084025.23 | |
|
DHCR7-related disorder
|
Benign (1) |
no assertion criteria provided
|
Nov 7, 2023 | RCV003891551.2 |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 16, 2016 | RCV002311593.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely benign
(May 02, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697852.1
First in ClinVar: Oct 30, 2017 Last updated: Oct 30, 2017 |
Comment:
Variant summary: The DHCR7 c.1341C>T (p.Asp447Asp) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no … (more)
Variant summary: The DHCR7 c.1341C>T (p.Asp447Asp) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may eliminate ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 399/117638 control chromosomes (6 homozygotes) at a frequency of 0.0033918, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301).Review publications, Jira_2003 and Wareham_2000, classify the variant as a "polymorphism," along with a publication indicating the variant to have been found in a cohort of SLOS patients and classified it as "polymorphism," as well as suggesting the variant may have co-occurred with a deleterious DHCR7 variant. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." Taken together, this variant is classified as "likely benign." (less)
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001870577.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 28972118)
|
|
|
Likely benign
(Aug 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002794941.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Likely benign
(Jun 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000846972.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Likely benign
(Jul 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV000608603.31
First in ClinVar: Oct 30, 2017 Last updated: Oct 20, 2024 |
Comment:
DHCR7: BP4, BP7, BS2
Number of individuals with the variant: 17
|
|
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Benign
(Apr 16, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000111525.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
|
|
|
Benign
(Jan 09, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000883710.1
First in ClinVar: Oct 30, 2017 Last updated: Oct 30, 2017 |
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001270466.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(Mar 29, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002069428.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000630072.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005218383.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980498.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
|
Likely benign
(Mar 28, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Smith-Lemli-Opitz syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002092995.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
|
Benign
(Nov 07, 2023)
|
no assertion criteria provided
Method: clinical testing
|
DHCR7-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000307640.3
First in ClinVar: Oct 02, 2016 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978043.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
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Comment:
Comment:
This variant is associated with the following publications: (PMID: 28972118)
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
DHCR7: BP4, BP7, BS2
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: The DHCR7 c.1341C>T (p.Asp447Asp) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may eliminate ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 399/117638 control chromosomes (6 homozygotes) at a frequency of 0.0033918, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301).Review publications, Jira_2003 and Wareham_2000, classify the variant as a "polymorphism," along with a publication indicating the variant to have been found in a cohort of SLOS patients and classified it as "polymorphism," as well as suggesting the variant may have co-occurred with a deleterious DHCR7 variant. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." Taken together, this variant is classified as "likely benign."
Comment:
This variant is associated with the following publications: (PMID: 28972118)
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
DHCR7: BP4, BP7, BS2
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Smith-Lemli-Opitz syndrome and the DHCR7 gene. | Jira PE | Annals of human genetics | 2003 | PMID: 12914579 |
| Mutations in the human DHCR7 gene. | Witsch-Baumgartner M | Human mutation | 2001 | PMID: 11241839 |
| Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome. | Waterham HR | Biochimica et biophysica acta | 2000 | PMID: 11111101 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DHCR7 | - | - | - | - |
Text-mined citations for rs139721775 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.