rs11615

chr19-45420395-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.629

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 -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	UniProt
ERCC1	NM_001983.4	c.354T>C	p.Asn118=	synonymous_variant	4/10	ENST00000300853.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC1	ENST00000300853.8	c.354T>C	p.Asn118=	synonymous_variant	4/10	1	NM_001983.4	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83875 AN: 151840 Hom.: 26919 Cov.: 31

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

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.: 37 AF XY: 0.416 AC XY: 301953 AN XY: 726166

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.: 31 AF XY: 0.554 AC XY: 41178 AN XY: 74276

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

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

Other links and lift over

dbSNP: rs11615; hg19: chr19-45923653;