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. The variant received -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
• Publications: 13 publications found

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]

ERCC3 Gene-Disease associations (from GenCC):

• trichothiodystrophy 2, photosensitive

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• xeroderma pigmentosum group B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp
• trichothiodystrophy 1, photosensitive

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum-Cockayne syndrome complex

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.229 AC: 9499 AN: 41432

American (AMR) AF: 0.515 AC: 7864 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3150 AN: 5132

South Asian (SAS) AF: 0.255 AC: 1226 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4257 AN: 10560

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24969 AN: 67922

Other (OTH) AF: 0.356 AC: 751 AN: 2110

Alfa AF: 0.377 Hom.: 4425

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
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs2276583; hg19: chr2-128014684;