VCV000129008.22 - ClinVar

NM_005236.3(ERCC4):c.2624A>G (p.Glu875Gly)

Germline

Classification

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.

(12)

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

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005236.3(ERCC4):c.2624A>G (p.Glu875Gly)

Variation ID: 129008 Accession: VCV000129008.22

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.12 16: 13948220 (GRCh38) [ NCBI UCSC ] 16: 14042077 (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	Jun 9, 2014	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_005236.3:c.2624A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005227.1:p.Glu875Gly	missense
NC_000016.10:g.13948220A>G
NC_000016.9:g.14042077A>G
NG_011442.1:g.33064A>G
LRG_463:g.33064A>G
LRG_463t1:c.2624A>G	LRG_463p1:p.Glu875Gly
	Q92889:p.Glu875Gly

... more HGVS ... less HGVS

Protein change

E875G

Other names

Canonical SPDI

NC_000016.10:13948219:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00579 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00547

1000 Genomes Project 0.00579

Trans-Omics for Precision Medicine (TOPMed) 0.01175

The Genome Aggregation Database (gnomAD) 0.01216

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01301

Exome Aggregation Consortium (ExAC) 0.01311

The Genome Aggregation Database (gnomAD), exomes 0.01330

Links

ClinGen: CA152759 UniProtKB: Q92889#VAR_013408 dbSNP: rs1800124 VarSome

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
Gene	OMIM	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.
ERCC4		-	-	GRCh38 GRCh37	771	865

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.
not specified	Benign (4)	criteria provided, single submitter	-	RCV000116989.16
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Apr 1, 2019	RCV000224428.6
Cockayne syndrome Fanconi anemia complementation group Q Xeroderma pigmentosum, group F	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV000228558.12
Hereditary cancer-predisposing syndrome	Likely benign (1)	criteria provided, single submitter	Dec 11, 2015	RCV000210773.2
Xeroderma pigmentosum, group F	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV001117767.7

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 (Dec 11, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Vantari Genetics Accession: SCV000267036.1 First in ClinVar: Apr 14, 2016 Last updated: Apr 14, 2016
Likely Benign (Aug 17, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000280899.1 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016	Comment: Converted during submission to Likely benign.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000310925.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Xeroderma pigmentosum, group F Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004017486.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Xeroderma pigmentosum, group F Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001275987.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (5) PubMed: 24004570‚ 18767034‚ 23407396‚ 24465539‚ 24728327 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 rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Benign (Apr 01, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001901105.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Comment: This variant is associated with the following publications: (PMID: 28051113, 17419091, 24728327, 20061190, 22374244, 15886521, 10479728, 24465539, 18767034, 28690523, 19626602, 24704021, 24004570)
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Fanconi anemia complementation group Q Xeroderma pigmentosum, group F Cockayne syndrome Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000288843.8 First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005217485.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002035124.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002036127.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151110.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000084972.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic
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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 rule this variant out of causing disease. Therefore, this variant is classified as benign.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.	Bodian DL	PloS one	2014	PMID: 24728327
Mutation analysis of the ERCC4/FANCQ gene in hereditary breast cancer.	Kohlhase S	PloS one	2014	PMID: 24465539
Inter-individual variation in nucleotide excision repair pathway is modulated by non-synonymous polymorphisms in ERCC4 and MBD4 genes.	Allione A	Mutation research	2013	PMID: 24004570
Polymorphisms of nucleotide excision repair genes predict melanoma survival.	Li C	The Journal of investigative dermatology	2013	PMID: 23407396
Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists.	Rajaraman P	International journal of cancer	2008	PMID: 18767034

Text-mined citations for rs1800124 ...

These 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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_005236.3(ERCC4):c.2624A>G (p.Glu875Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1800124 ...