rs4253212

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000124.4(ERCC6):c.3778+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,610,482 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 188 hom. )

Consequence

ERCC6
NM_000124.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.33

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-49470166-G-A is Benign according to our data. Variant chr10-49470166-G-A is described in ClinVar as Benign. ClinVar VariationId is 255166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6	NM_000124.4 link	c.3778+16C>T		intron_variant	Intron 18 of 20	ENST00000355832.10	NP_000115.1	Q03468-1Q59FF6
ERCC6	NM_001346440.2 link	c.3778+16C>T		intron_variant	Intron 18 of 20		NP_001333369.1	Q03468-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 link	c.3778+16C>T		intron_variant	Intron 18 of 20	1	NM_000124.4	ENSP00000348089.5		Q03468-1

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

736

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.0115

AC:

2884

AN:

251178

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00327

AC:

4763

AN:

1458206

Hom.:

188

Cov.:

AF XY:

0.00314

AC XY:

2278

AN XY:

725712

show subpopulations

African (AFR)

AF:

0.000569

AC:

AN:

33416

American (AMR)

AF:

0.0178

AC:

796

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000728

AC:

AN:

26112

East Asian (EAS)

AF:

0.0842

AC:

3342

AN:

39682

South Asian (SAS)

AF:

0.00230

AC:

198

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000685

AC:

AN:

1108718

Other (OTH)

AF:

0.00518

AC:

312

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

249

499

748

998

1247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00483

AC:

735

AN:

152276

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41562

American (AMR)

AF:

0.00680

AC:

104

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.108

AC:

560

AN:

5178

South Asian (SAS)

AF:

0.00311

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68024

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00168

Hom.:

Bravo

AF:

0.00614

Asia WGS

AF:

0.0380

AC:

131

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.88

CADD

Benign

0.12

(source)

DANN

Benign

0.67

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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