rs4150407

chr2-127292055-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.471+555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 183,616 control chromosomes in the GnomAD database, including 20,393 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 0.47 (17020 hom., cov: 32)
  • Exomes 𝑓: 0.43 (3373 hom.)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC3	NM_000122.2	c.471+555A>G		intron_variant		ENST00000285398.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC3	ENST00000285398.7	c.471+555A>G		intron_variant		1	NM_000122.2	P1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71245 AN: 151950 Hom.: 16993 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.430 AC: 13578 AN: 31546 Hom.: 3373 Cov.: 0 AF XY: 0.423 AC XY: 6941 AN XY: 16416

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.469 AC: 71321 AN: 152070 Hom.: 17020 Cov.: 32 AF XY: 0.470 AC XY: 34928 AN XY: 74334

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.469

Alfa AF: 0.496 Hom.: 3017

Bravo AF: 0.488

Asia WGS AF: 0.457 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.52

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: rs4150407; hg19: chr2-128049631; COSMIC: COSV53430279; COSMIC: COSV53430279;