rs3213255

Positions:

• chr19-43573355-G-A
• chr19-43573355-G-C
• chr19-43573355-G-T

Variant summary

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

The NM_006297.3(XRCC1):​c.144+1555C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,968 control chromosomes in the GnomAD database, including 28,191 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 0.61 (28191 hom., cov: 31)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.144+1555C>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+1555C>T		intron_variant		1	NM_006297.3	ENSP00000262887	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91937 AN: 151852 Hom.: 28176 Cov.: 31

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.605 AC: 91993 AN: 151968 Hom.: 28191 Cov.: 31 AF XY: 0.609 AC XY: 45192 AN XY: 74260

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.614

Alfa AF: 0.589 Hom.: 14915

Bravo AF: 0.621

Asia WGS AF: 0.732 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.74

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: rs3213255; hg19: chr19-44077507;