rs4150506

Positions:

• chr2-127262970-G-A
• chr2-127262970-G-T

Variant summary

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

The NM_000122.2(ERCC3):​c.1946-1624C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,084 control chromosomes in the GnomAD database, including 2,967 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 0.18 (2967 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC3	NM_000122.2	c.1946-1624C>T		intron_variant		ENST00000285398.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC3	ENST00000285398.7	c.1946-1624C>T		intron_variant		1	NM_000122.2	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27649 AN: 151950 Hom.: 2960 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.182 AC: 27661 AN: 152068 Hom.: 2967 Cov.: 32 AF XY: 0.186 AC XY: 13852 AN XY: 74320

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.198

Alfa AF: 0.183 Hom.: 459

Bravo AF: 0.166

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.12

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: rs4150506; hg19: chr2-128020546;