rs3213368

Positions:

• chr19-43551492-G-A
• chr19-43551492-G-C

Variant summary

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

The NM_006297.3(XRCC1):​c.1199+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,268,608 control chromosomes in the GnomAD database, including 4,501 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 0.089 (770 hom., cov: 33)
  • Exomes 𝑓: 0.073 (3731 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.1199+79C>T		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.1199+79C>T		intron_variant		1	NM_006297.3	P1
XRCC1	ENST00000543982.5	c.1106+79C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13503 AN: 152090 Hom.: 766 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0841

GnomAD4 exome AF: 0.0728 AC: 81230 AN: 1116400 Hom.: 3731 AF XY: 0.0709 AC XY: 40337 AN XY: 568800

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0631

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0494

Gnomad4 FIN exome AF: 0.0917

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.0752

GnomAD4 genome AF: 0.0888 AC: 13509 AN: 152208 Hom.: 770 Cov.: 33 AF XY: 0.0907 AC XY: 6747 AN XY: 74418

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0744 Hom.: 62

Bravo AF: 0.0957

Asia WGS AF: 0.0890 AC: 308 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	4.1
DANN	Benign	0.69

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: rs3213368; hg19: chr19-44055644; COSMIC: COSV53452431; COSMIC: COSV53452431;