rs2293036

Positions:

• chr19-43553896-G-A

Variant summary

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

The NM_006297.3(XRCC1):​c.415-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 483,326 control chromosomes in the GnomAD database, including 2,669 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 0.073 (624 hom., cov: 32)
  • Exomes 𝑓: 0.085 (2045 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.415-213C>T		intron_variant		ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.415-213C>T		intron_variant		1	NM_006297.3	ENSP00000262887	P1
	ENST00000597119.1	n.83+369G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11128 AN: 152100 Hom.: 624 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0852 AC: 28198 AN: 331108 Hom.: 2045 AF XY: 0.0851 AC XY: 14344 AN XY: 168600

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0633

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.0362

Gnomad4 NFE exome AF: 0.0618

Gnomad4 OTH exome AF: 0.0831

GnomAD4 genome AF: 0.0731 AC: 11130 AN: 152218 Hom.: 624 Cov.: 32 AF XY: 0.0738 AC XY: 5491 AN XY: 74420

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0853

Alfa AF: 0.0667 Hom.: 85

Bravo AF: 0.0798

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.8
DANN	Benign	0.53

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: rs2293036; hg19: chr19-44058048;