Variant rs11615 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001983.4(ERCC1):c.354T>C(p.Asn118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,611,696 control chromosomes in the GnomAD database, including 163,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 26981 hom., cov: 31)

Exomes 𝑓: 0.42 ( 136082 hom. )

Consequence

ERCC1
NM_001983.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.629

Variant links:

Genes affected

ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

ERCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 19-45420395-A-G is Benign according to our data. Variant chr19-45420395-A-G is described in ClinVar as [Benign]. Clinvar id is 225945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45420395-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.629 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC1	NM_001983.4 linkuse as main transcript	c.354T>C	p.Asn118=	synonymous_variant	4/10	ENST00000300853.8	NP_001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC1	ENST00000300853.8 linkuse as main transcript	c.354T>C	p.Asn118=	synonymous_variant	4/10	1	NM_001983.4	ENSP00000300853	P1	P07992-1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83875

AN:

151840

Hom.:

26919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.518

GnomAD3 exomes

AF:

0.501

AC:

125107

AN:

249686

Hom.:

35330

AF XY:

0.485

AC XY:

65375

AN XY:

134914

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.705

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.734

Gnomad SAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.374

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.415

AC:

606069

AN:

1459736

Hom.:

136082

Cov.:

AF XY:

0.416

AC XY:

301953

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.893

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.553

AC:

83997

AN:

151960

Hom.:

26981

Cov.:

AF XY:

0.554

AC XY:

41178

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.875

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.414

Hom.:

34822

Bravo

AF:

0.584

Asia WGS

AF:

0.667

AC:

2322

AN:

3478

EpiCase

AF:

0.381

EpiControl

AF:

0.384

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.010

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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