rs2229760

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000124.4(ERCC6):c.2751C>T(p.Gly917Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,566 control chromosomes in the GnomAD database, including 122,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8661 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113966 hom. )

Consequence

ERCC6
NM_000124.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.397

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

Cockayne spectrum with or without cerebrooculofacioskeletal syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Cockayne syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Myriad Women’s Health, Orphanet, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
UV-sensitive syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
COFS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
UV-sensitive syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
premature ovarian failure 11
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ERCC6 links:

ENSG00000235939 (HGNC:):

ENSG00000235939 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 10-49472987-G-A is Benign according to our data. Variant chr10-49472987-G-A is described in ClinVar as Benign. ClinVar VariationId is 129015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.397 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6	NM_000124.4 link	c.2751C>T	p.Gly917Gly	synonymous_variant	Exon 15 of 21	ENST00000355832.10	NP_000115.1
ERCC6	NM_001346440.2 link	c.2751C>T	p.Gly917Gly	synonymous_variant	Exon 15 of 21		NP_001333369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 link	c.2751C>T	p.Gly917Gly	synonymous_variant	Exon 15 of 21	1	NM_000124.4	ENSP00000348089.5

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47908

AN:

151970

Hom.:

8670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.331

GnomAD2 exomes

AF:

0.340

AC:

85285

AN:

250862

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.388

AC:

567413

AN:

1461478

Hom.:

113966

Cov.:

AF XY:

0.385

AC XY:

280045

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.137

AC:

4585

AN:

33474

American (AMR)

AF:

0.279

AC:

12480

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8663

AN:

26130

East Asian (EAS)

AF:

0.311

AC:

12355

AN:

39670

South Asian (SAS)

AF:

0.249

AC:

21488

AN:

86238

European-Finnish (FIN)

AF:

0.383

AC:

20453

AN:

53406

Middle Eastern (MID)

AF:

0.366

AC:

2111

AN:

5768

European-Non Finnish (NFE)

AF:

0.417

AC:

463247

AN:

1111704

Other (OTH)

AF:

0.365

AC:

22031

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19171

38342

57513

76684

95855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14036

28072

42108

56144

70180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.315

AC:

47889

AN:

152088

Hom.:

8661

Cov.:

AF XY:

0.312

AC XY:

23175

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.140

AC:

5811

AN:

41526

American (AMR)

AF:

0.311

AC:

4750

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1135

AN:

3470

East Asian (EAS)

AF:

0.318

AC:

1643

AN:

5168

South Asian (SAS)

AF:

0.255

AC:

1227

AN:

4808

European-Finnish (FIN)

AF:

0.377

AC:

3984

AN:

10558

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.413

AC:

28067

AN:

67964

Other (OTH)

AF:

0.329

AC:

694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1595

3191

4786

6382

7977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.382

Hom.:

22855

Bravo

AF:

0.305

Asia WGS

AF:

0.273

AC:

949

AN:

3476

EpiCase

AF:

0.419

EpiControl

AF:

0.418

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Claritas Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

COFS syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cerebrooculofacioskeletal syndrome 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cockayne syndrome type 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cockayne syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

UV-sensitive syndrome 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DE SANCTIS-CACCHIONE SYNDROME

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Macular degeneration

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.3

(source)

DANN

Benign

0.86

PhyloP100

-0.40

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over