rs2276583

Variant names:

• chr2-127257108-G-A
• rs2276583
• NM_000122.2:c.*488C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127257108-G-A
• chr2-127257108-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000122.2(ERCC3):​c.*488C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,918 control chromosomes in the GnomAD database, including 10,180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10180 hom., cov: 31)
• Consequence: ERCC3 NM_000122.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC3	NM_000122.2	c.*488C>T		downstream_gene_variant		ENST00000285398.7	NP_000113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC3	ENST00000285398.7	c.*488C>T		downstream_gene_variant		1	NM_000122.2	ENSP00000285398.2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53428 AN: 151800 Hom.: 10172 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.352 AC: 53465 AN: 151918 Hom.: 10180 Cov.: 31 AF XY: 0.358 AC XY: 26552 AN XY: 74242

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.356

Alfa AF: 0.381 Hom.: 3645

Bravo AF: 0.362

Asia WGS AF: 0.434 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.70
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2276583; hg19: chr2-128014684;