rs171140

chr19-45361744-C-A

Variant summary

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

The NM_000400.4(ERCC2):c.1119-102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 868,646 control chromosomes in the GnomAD database, including 147,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (32321 hom., cov: 31)
  • Exomes 𝑓: 0.56 (115287 hom.)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.161

Genes affected

ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-45361744-C-A is Benign according to our data. Variant chr19-45361744-C-A is described in ClinVar as [Benign]. Clinvar id is 135529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC2	NM_000400.4	c.1119-102G>T		intron_variant		ENST00000391945.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10	c.1119-102G>T		intron_variant		1	NM_000400.4	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96572 AN: 151800 Hom.: 32270 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.595

GnomAD3 exomes AF: 0.581 AC: 117148 AN: 201574 Hom.: 34430 AF XY: 0.579 AC XY: 62969 AN XY: 108770

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.511

Gnomad SAS exome AF: 0.604

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.564 AC: 404426 AN: 716726 Hom.: 115287 Cov.: 9 AF XY: 0.566 AC XY: 215607 AN XY: 380928

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.636 AC: 96676 AN: 151920 Hom.: 32321 Cov.: 31 AF XY: 0.634 AC XY: 47050 AN XY: 74248

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.594

Alfa AF: 0.564 Hom.: 41452

Bravo AF: 0.643

Asia WGS AF: 0.561 AC: 1956 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	9.5
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs171140; hg19: chr19-45865002; COSMIC: COSV55538511; COSMIC: COSV55538511;