rs3213266

Positions:

• chr19-43571484-G-A

Variant summary

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

The ENST00000262887.10(XRCC1):​c.144+3426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,162 control chromosomes in the GnomAD database, including 960 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 0.10 (960 hom., cov: 33)
• Consequence: XRCC1 ENST00000262887.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.144+3426C>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.144+3426C>T		intron_variant		1	NM_006297.3	ENSP00000262887	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15661 AN: 152044 Hom.: 956 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0988

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15664 AN: 152162 Hom.: 960 Cov.: 33 AF XY: 0.105 AC XY: 7777 AN XY: 74374

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0461

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.0977

Alfa AF: 0.0974 Hom.: 330

Bravo AF: 0.110

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.68

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: rs3213266; hg19: chr19-44075636;