2-127283339-T-C

Variant names:

• chr2-127283339-T-C
• rs4150441
• NM_000122.2:c.1343-2708A>G

Variant summary

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

The NM_000122.2(ERCC3):​c.1343-2708A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,946 control chromosomes in the GnomAD database, including 11,588 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 0.38 (11588 hom., cov: 31)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.99).
• 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 rank	MANE	Protein	UniProt
ERCC3	NM_000122.2	c.1343-2708A>G		intron_variant	Intron 8 of 14	ENST00000285398.7	NP_000113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC3	ENST00000285398.7	c.1343-2708A>G		intron_variant	Intron 8 of 14	1	NM_000122.2	ENSP00000285398.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57410 AN: 151828 Hom.: 11578 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.378 AC: 57452 AN: 151946 Hom.: 11588 Cov.: 31 AF XY: 0.382 AC XY: 28392 AN XY: 74262

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.390

Alfa AF: 0.387 Hom.: 1449

Bravo AF: 0.390

Asia WGS AF: 0.437 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.43

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: rs4150441; hg19: chr2-128040915;