rs16979802

chr19-45416697-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001983.4(ERCC1):c.602+124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 727,248 control chromosomes in the GnomAD database, including 2,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (444 hom., cov: 31)
  • Exomes 𝑓: 0.084 (2510 hom.)
• Consequence: ERCC1 NM_001983.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.461

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-45416697-G-C is Benign according to our data. Variant chr19-45416697-G-C is described in ClinVar as [Benign]. Clinvar id is 1245816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC1	NM_001983.4	c.602+124C>G		intron_variant		ENST00000300853.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC1	ENST00000300853.8	c.602+124C>G		intron_variant		1	NM_001983.4	P1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10210 AN: 151550 Hom.: 445 Cov.: 31

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0839 AC: 48290 AN: 575580 Hom.: 2510 Cov.: 7 AF XY: 0.0850 AC XY: 26210 AN XY: 308382

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.0779

Gnomad4 ASJ exome AF: 0.0937

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.0570

Gnomad4 NFE exome AF: 0.0750

Gnomad4 OTH exome AF: 0.0799

GnomAD4 genome AF: 0.0673 AC: 10202 AN: 151668 Hom.: 444 Cov.: 31 AF XY: 0.0678 AC XY: 5027 AN XY: 74118

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.0761

Alfa AF: 0.0610 Hom.: 40

Bravo AF: 0.0662

Asia WGS AF: 0.127 AC: 439 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.9
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs16979802; hg19: chr19-45919955; COSMIC: COSV50005117; COSMIC: COSV50005117;