19-43554989-G-T

Position:

• chr19-43554989-G-T

Variant summary

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

The ENST00000262887.10(XRCC1):​c.256-185C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 512,484 control chromosomes in the GnomAD database, including 29,002 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 0.31 (7529 hom., cov: 31)
  • Exomes 𝑓: 0.34 (21473 hom.)
• Consequence: XRCC1 ENST00000262887.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.256-185C>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.256-185C>A		intron_variant		1	NM_006297.3	ENSP00000262887	P1
	ENST00000597119.1	n.84-28G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47092 AN: 151824 Hom.: 7518 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.340 AC: 122496 AN: 360542 Hom.: 21473 Cov.: 5 AF XY: 0.342 AC XY: 64258 AN XY: 187640

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.310 AC: 47121 AN: 151942 Hom.: 7529 Cov.: 31 AF XY: 0.307 AC XY: 22783 AN XY: 74274

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.308

Alfa AF: 0.326 Hom.: 3821

Bravo AF: 0.305

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.96
DANN	Benign	0.83

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: rs1799778; hg19: chr19-44059141; COSMIC: COSV53450734; COSMIC: COSV53450734;