rs4150416

Positions:

• chr2-127288972-C-A

Variant summary

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

The NM_000122.2(ERCC3):​c.823-108G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 936,498 control chromosomes in the GnomAD database, including 225,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34350 hom., cov: 32)
  • Exomes 𝑓: 0.69 (191128 hom.)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

Genes affected

ERCC3 (HGNC:3435): (ERCC excision repair 3, TFIIH core complex helicase subunit) This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne's syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-127288972-C-A is Benign according to our data. Variant chr2-127288972-C-A is described in ClinVar as [Benign]. Clinvar id is 1245290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC3	NM_000122.2	c.823-108G>T		intron_variant		ENST00000285398.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC3	ENST00000285398.7	c.823-108G>T		intron_variant		1	NM_000122.2	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101201 AN: 151972 Hom.: 34321 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.691 AC: 542260 AN: 784408 Hom.: 191128 AF XY: 0.690 AC XY: 286820 AN XY: 415844

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.666 AC: 101286 AN: 152090 Hom.: 34350 Cov.: 32 AF XY: 0.674 AC XY: 50079 AN XY: 74346

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.669

Alfa AF: 0.665 Hom.: 6991

Bravo AF: 0.665

Asia WGS AF: 0.848 AC: 2945 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

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.024
DANN	Benign	0.50

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: rs4150416; hg19: chr2-128046548;