rs4150403

Positions:

• chr2-127292492-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000122.2(ERCC3):​c.471+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 802,618 control chromosomes in the GnomAD database, including 2,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (334 hom., cov: 32)
  • Exomes 𝑓: 0.066 (1712 hom.)
• Consequence: ERCC3 NM_000122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.699

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-127292492-C-T is Benign according to our data. Variant chr2-127292492-C-T is described in ClinVar as [Benign]. Clinvar id is 1234691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC3	NM_000122.2	c.471+118G>A		intron_variant		ENST00000285398.7	NP_000113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC3	ENST00000285398.7	c.471+118G>A		intron_variant		1	NM_000122.2	ENSP00000285398.2

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8566 AN: 152070 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0643

GnomAD4 exome AF: 0.0660 AC: 42918 AN: 650430 Hom.: 1712 Cov.: 8 AF XY: 0.0641 AC XY: 22656 AN XY: 353284

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0945

Gnomad4 EAS exome AF: 0.000138

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.0974

Gnomad4 NFE exome AF: 0.0820

Gnomad4 OTH exome AF: 0.0680

GnomAD4 genome AF: 0.0563 AC: 8562 AN: 152188 Hom.: 334 Cov.: 32 AF XY: 0.0547 AC XY: 4066 AN XY: 74392

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0962

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0636

Alfa AF: 0.0773 Hom.: 637

Bravo AF: 0.0506

Asia WGS AF: 0.00982 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4150403; hg19: chr2-128050068;