rs3213245

chr19-43575535-G-Achr19-43575535-G-T

Variant summary

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

The ENST00000600242.1(ENSG00000269583):n.463G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,467,464 control chromosomes in the GnomAD database, including 274,986 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 0.61 (28318 hom., cov: 31)
  • Exomes 𝑓: 0.60 (246668 hom.)
• Consequence: ENST00000600242.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

(HGNC:):

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINLYP	XM_047438830.1	c.-1585G>A		5_prime_UTR_variant	1/5
XRCC1	NM_006297.3			upstream_gene_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000600242.1	n.463G>A		non_coding_transcript_exon_variant	2/2	4
XRCC1	ENST00000262887.10			upstream_gene_variant		1	NM_006297.3	P1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92148 AN: 151734 Hom.: 28305 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.617

GnomAD3 exomes AF: 0.650 AC: 128956 AN: 198250 Hom.: 42815 AF XY: 0.641 AC XY: 69690 AN XY: 108644

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.889

Gnomad SAS exome AF: 0.614

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.604 AC: 795285 AN: 1315610 Hom.: 246668 Cov.: 18 AF XY: 0.603 AC XY: 392843 AN XY: 651374

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.894

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.607 AC: 92204 AN: 151854 Hom.: 28318 Cov.: 31 AF XY: 0.610 AC XY: 45260 AN XY: 74200

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.618

Alfa AF: 0.591 Hom.: 4917

Bravo AF: 0.624

Asia WGS AF: 0.733 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.2
Dann	Benign	0.95

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: rs3213245; hg19: chr19-44079687; COSMIC: COSV53448643; COSMIC: COSV53448643;