19-43551746-C-T

Position:

• chr19-43551746-C-T

Variant summary

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

The NM_006297.3(XRCC1):​c.1083-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,315,072 control chromosomes in the GnomAD database, including 280,867 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 0.69 (36017 hom., cov: 31)
  • Exomes 𝑓: 0.65 (244850 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.1083-59G>A		intron_variant		ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.1083-59G>A		intron_variant		1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982.5	c.990-59G>A		intron_variant		2		ENSP00000443671.1
XRCC1	ENST00000597811.5	n.*197-59G>A		intron_variant		5		ENSP00000470391.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104271 AN: 151756 Hom.: 35982 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.647 AC: 752408 AN: 1163198 Hom.: 244850 AF XY: 0.647 AC XY: 383033 AN XY: 592404

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.725

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.633

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.687 AC: 104352 AN: 151874 Hom.: 36017 Cov.: 31 AF XY: 0.691 AC XY: 51271 AN XY: 74200

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.688

Alfa AF: 0.682 Hom.: 5931

Bravo AF: 0.691

Asia WGS AF: 0.697 AC: 2427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs25486; hg19: chr19-44055898;