2-127280968-T-C

Position:

• chr2-127280968-T-C

Variant summary

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

The NM_000122.2(ERCC3):​c.1343-337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 477,276 control chromosomes in the GnomAD database, including 41,526 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 0.37 (11286 hom., cov: 32)
  • Exomes 𝑓: 0.42 (30240 hom.)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC3	NM_000122.2	c.1343-337A>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.1343-337A>G		intron_variant		1	NM_000122.2	ENSP00000285398.2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56393 AN: 151932 Hom.: 11280 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.422 AC: 137283 AN: 325224 Hom.: 30240 Cov.: 0 AF XY: 0.419 AC XY: 70185 AN XY: 167454

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.680

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.371 AC: 56417 AN: 152052 Hom.: 11286 Cov.: 32 AF XY: 0.375 AC XY: 27876 AN XY: 74316

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.382

Alfa AF: 0.379 Hom.: 5033

Bravo AF: 0.381

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4150454; hg19: chr2-128038544;