rs25484

Positions:

• chr19-43546814-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006297.3(XRCC1):​c.1293+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,596,984 control chromosomes in the GnomAD database, including 25,306 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 0.16 (2097 hom., cov: 31)
  • Exomes 𝑓: 0.17 (23209 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.1293+70A>G		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.1293+70A>G		intron_variant		1	NM_006297.3	P1
XRCC1	ENST00000543982.5	c.1200+70A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24744 AN: 151550 Hom.: 2099 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.150 AC: 36308 AN: 242772 Hom.: 3095 AF XY: 0.154 AC XY: 20146 AN XY: 130968

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0916

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.000928

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.174 AC: 251997 AN: 1445316 Hom.: 23209 Cov.: 33 AF XY: 0.174 AC XY: 124849 AN XY: 716316

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.0936

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.000457

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.163 AC: 24756 AN: 151668 Hom.: 2097 Cov.: 31 AF XY: 0.161 AC XY: 11919 AN XY: 74090

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.153

Alfa AF: 0.178 Hom.: 542

Bravo AF: 0.157

Asia WGS AF: 0.0610 AC: 214 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	11
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs25484; hg19: chr19-44050966;