19-43556501-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.256-1697C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,198 control chromosomes in the GnomAD database, including 631 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 0.074 (631 hom., cov: 32)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.256-1697C>G		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.256-1697C>G		intron_variant		1	NM_006297.3	P1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11210 AN: 152080 Hom.: 631 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.0737 AC: 11211 AN: 152198 Hom.: 631 Cov.: 32 AF XY: 0.0743 AC XY: 5530 AN XY: 74412

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0313 Hom.: 17

Bravo AF: 0.0805

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.62

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: rs3213344; hg19: chr19-44060653;