rs731420

Positions:

• chr19-43553820-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.415-137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 663,654 control chromosomes in the GnomAD database, including 793 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 0.054 (311 hom., cov: 31)
  • Exomes 𝑓: 0.037 (482 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.415-137C>T		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.415-137C>T		intron_variant		1	NM_006297.3	P1
	ENST00000597119.1	n.83+293G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8269 AN: 152074 Hom.: 309 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0368 AC: 18800 AN: 511460 Hom.: 482 Cov.: 7 AF XY: 0.0357 AC XY: 9366 AN XY: 262088

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0363

Gnomad4 ASJ exome AF: 0.0570

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.0246

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0438

GnomAD4 genome AF: 0.0544 AC: 8284 AN: 152194 Hom.: 311 Cov.: 31 AF XY: 0.0544 AC XY: 4050 AN XY: 74432

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0403

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0292

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0376 Hom.: 42

Bravo AF: 0.0591

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.35

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: rs731420; hg19: chr19-44057972;