Variant rs11101139 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000124.4(ERCC6):c.2170-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,229,700 control chromosomes in the GnomAD database, including 3,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 346 hom., cov: 32)

Exomes 𝑓: 0.067 ( 2906 hom. )

Consequence

ERCC6
NM_000124.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.419

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-49478508-G-A is Benign according to our data. Variant chr10-49478508-G-A is described in ClinVar as [Benign]. Clinvar id is 255164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0833 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.2170-38C>T		intron_variant		ENST00000355832.10	NP_000115.1
ERCC6	NM_001346440.2 linkuse as main transcript	c.2170-38C>T		intron_variant			NP_001333369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC6	ENST00000355832.10 linkuse as main transcript	c.2170-38C>T		intron_variant		1	NM_000124.4	ENSP00000348089	P1	Q03468-1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8493

AN:

150422

Hom.:

346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.0692

Gnomad ASJ

AF:

0.0900

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.0705

GnomAD3 exomes

AF:

0.0535

AC:

13205

AN:

246658

Hom.:

491

AF XY:

0.0540

AC XY:

7224

AN XY:

133734

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.0368

Gnomad ASJ exome

AF:

0.0896

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.0335

Gnomad NFE exome

AF:

0.0824

Gnomad OTH exome

AF:

0.0669

GnomAD4 exome

AF:

0.0667

AC:

72021

AN:

1079166

Hom.:

2906

Cov.:

AF XY:

0.0659

AC XY:

36583

AN XY:

554958

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0886

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.0798

Gnomad4 OTH exome

AF:

0.0640

GnomAD4 genome

AF:

0.0564

AC:

8487

AN:

150534

Hom.:

346

Cov.:

AF XY:

0.0532

AC XY:

3901

AN XY:

73378

show subpopulations

Gnomad4 AFR

AF:

0.0151

Gnomad4 AMR

AF:

0.0689

Gnomad4 ASJ

AF:

0.0900

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0290

Gnomad4 NFE

AF:

0.0851

Gnomad4 OTH

AF:

0.0697

Alfa

AF:

0.0754

Hom.:

Bravo

AF:

0.0565

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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