ClinVar Genomic variation as it relates to human health
NM_176824.3(BBS7):c.712_715del (p.Arg238fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_176824.3(BBS7):c.712_715del (p.Arg238fs)
Variation ID: 281626 Accession: VCV000281626.59
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: 4q27 4: 121854707-121854710 (GRCh38) [ NCBI UCSC ] 4: 122775862-122775865 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 8, 2017 Apr 15, 2024 Jan 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_176824.3:c.712_715del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_789794.1:p.Arg238fs frameshift NM_176824.3:c.712_715delAGAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_018190.4:c.712_715del NP_060660.2:p.Arg238fs frameshift NM_176824.2:c.712_715del NC_000004.12:g.121854707CT[1] NC_000004.11:g.122775862CT[1] NG_009111.1:g.20776AG[1] - Protein change
- R238fs
- Other names
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- Canonical SPDI
- NC_000004.12:121854706:CTCTCT:CT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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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. |
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BBS7 | - | - |
GRCh38 GRCh37 |
668 | 708 |
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. |
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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 3, 2021 | RCV000424630.25 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 28, 2023 | RCV000820069.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 7, 2018 | RCV001075009.2 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jul 18, 2023 | RCV001770227.13 | |
Pathogenic (1) |
no assertion criteria provided
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May 10, 2023 | RCV003228920.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2024 | RCV003409402.5 |
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. |
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Pathogenic
(Nov 10, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511151.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Jul 09, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000332505.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Feb 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001240619.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447415.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Global developmental delay (present) , Obesity (present) , Abnormality of the cardiovascular system (present) , Hydrometrocolpos (present) , Median cleft upper lip (present) , Abnormality … (more)
Global developmental delay (present) , Obesity (present) , Abnormality of the cardiovascular system (present) , Hydrometrocolpos (present) , Median cleft upper lip (present) , Abnormality of the face (present) , Postaxial hand polydactyly (present) (less)
Sex: female
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Pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755106.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Indication for testing: Bardet-Biedl syndrome
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Pathogenic
(Aug 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 7
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV002764833.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Number of individuals with the variant: 1
Clinical Features:
Abnormality of the eye (present) , Renal insufficiency (present) , Polydactyly (present)
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Pathogenic
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 7
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002779950.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011698.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 7
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047919.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The c.712_715del (p.Arg238GlufsTer59) frameshift variant in BBS7 gene has been has been observed to be homozygous or in combination with another BBS7 variant in individuals … (more)
The c.712_715del (p.Arg238GlufsTer59) frameshift variant in BBS7 gene has been has been observed to be homozygous or in combination with another BBS7 variant in individuals with Bardet-Biedl Syndrome (Ece et al., 2015; Bin et al., 2009). The p.Pro790GlnfsTer98 variant is reported with the allele frequency (0.005%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Arginine 238, changes this amino acid to Glutamic Acid residue, and creates a premature Stop codon at position 59 of the new reading frame, denoted p.Arg238GlufsTer59. Loss-of-function variants in BBS7 are known to be pathogenic (Badano et al., 2003). For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Obesity (present) , Subvalvular aortic stenosis (present)
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Pathogenic
(Jul 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 7
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004214154.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 09, 2020)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 7
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002024539.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000960763.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg238Glufs*59) in the BBS7 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg238Glufs*59) in the BBS7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS7 are known to be pathogenic (PMID: 12567324, 19402160, 21209035, 31196119). This variant is present in population databases (rs760165634, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with Bardet-Biedl Syndrome (PMID: 19402160, 26518167). ClinVar contains an entry for this variant (Variation ID: 281626). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 09, 2024)
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criteria provided, single submitter
Method: clinical testing
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BBS7-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004116024.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The BBS7 c.712_715delAGAG variant is predicted to result in a frameshift and premature protein termination (p.Arg238Glufs*59). This variant has been reported in the homozygous or … (more)
The BBS7 c.712_715delAGAG variant is predicted to result in a frameshift and premature protein termination (p.Arg238Glufs*59). This variant has been reported in the homozygous or compound heterozygous state in individuals with Bardet-Biedl syndrome (Bin et al. 2009. PubMed ID: 19402160; Ece Solmaz et al. 2015. PubMed ID: 26518167), and chain terminating variants in BBS7 are a well-established mechanism of pathogenicity. This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jun 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247390.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(May 10, 2023)
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no assertion criteria provided
Method: research
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Bardet-Biedl syndrome 1
Affected status: yes
Allele origin:
maternal,
paternal,
biparental
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Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago
Accession: SCV003926572.1
First in ClinVar: May 27, 2023 Last updated: May 27, 2023 |
Observation 1: Observation 2: Observation 3: |
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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. |
Citations for germline classification of this variant
HelpText-mined citations for rs760165634 ...
HelpRecord last updated Apr 20, 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.