10-49471035-G-A

Position:

chr10-49471035-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000124.4(ERCC6):c.3010C>T(p.Leu1004Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,614,068 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1004L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0054 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 142 hom. )

Consequence

ERCC6
NM_000124.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 8.09

Variant links:

Genes affected

ERCC6 (HGNC:3438): (ERCC excision repair 6, chromatin remodeling factor) This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]

ERCC6 links:

ERCC6 (HGNC:):

ERCC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 10-49471035-G-A is Benign according to our data. Variant chr10-49471035-G-A is described in ClinVar as [Benign]. Clinvar id is 194696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-49471035-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC6	NM_000124.4 linkuse as main transcript	c.3010C>T	p.Leu1004Leu	synonymous_variant	17/21	ENST00000355832.10	NP_000115.1	Q03468-1Q59FF6
ERCC6	NM_001346440.2 linkuse as main transcript	c.3010C>T	p.Leu1004Leu	synonymous_variant	17/21		NP_001333369.1	Q03468-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 linkuse as main transcript	c.3010C>T	p.Leu1004Leu	synonymous_variant	17/21	1	NM_000124.4	ENSP00000348089.5		Q03468-1

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

821

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0756

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.0123

AC:

3097

AN:

251200

Hom.:

103

AF XY:

0.0107

AC XY:

1450

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0789

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.000749

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00367

AC:

5359

AN:

1461758

Hom.:

142

Cov.:

AF XY:

0.00349

AC XY:

2537

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0675

Gnomad4 SAS exome

AF:

0.000614

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.000188

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.00537

AC:

818

AN:

152310

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0754

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00641

Asia WGS

AF:

0.0230

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 02, 2019	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Cerebrooculofacioskeletal syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Age related macular degeneration 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Cockayne syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

8.1

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over