chr19-43551430-C-T

Position:

• chr19-43551430-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.1199+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 713,160 control chromosomes in the GnomAD database, including 17,909 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 0.21 (3496 hom., cov: 32)
  • Exomes 𝑓: 0.22 (14413 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.1199+141G>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.1199+141G>A		intron_variant		1	NM_006297.3	ENSP00000262887.5
XRCC1	ENST00000543982.5	c.1106+141G>A		intron_variant		2		ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31917 AN: 152050 Hom.: 3496 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.219 AC: 122656 AN: 560992 Hom.: 14413 AF XY: 0.221 AC XY: 64850 AN XY: 293958

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.210 AC: 31953 AN: 152168 Hom.: 3496 Cov.: 32 AF XY: 0.210 AC XY: 15603 AN XY: 74360

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.206

Alfa AF: 0.224 Hom.: 460

Bravo AF: 0.194

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.87

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: rs2139720; hg19: chr19-44055582; COSMIC: COSV53451539; COSMIC: COSV53451539;