rs2134794

Positions:

• chr2-127273303-A-C

Variant summary

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

The NM_000122.2(ERCC3):​c.1731-342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,142 control chromosomes in the GnomAD database, including 3,281 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 0.20 (3281 hom., cov: 31)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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 (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC3	NM_000122.2	c.1731-342T>G		intron_variant		ENST00000285398.7	NP_000113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC3	ENST00000285398.7	c.1731-342T>G		intron_variant		1	NM_000122.2	ENSP00000285398	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30394 AN: 152024 Hom.: 3272 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.200 AC: 30421 AN: 152142 Hom.: 3281 Cov.: 31 AF XY: 0.203 AC XY: 15121 AN XY: 74386

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.208

Alfa AF: 0.202 Hom.: 637

Bravo AF: 0.187

Asia WGS AF: 0.314 AC: 1090 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	2.5
DANN	Benign	0.62

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: rs2134794; hg19: chr2-128030879;