chr19-43545709-G-T

Position:

• chr19-43545709-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.1621+109C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,435,060 control chromosomes in the GnomAD database, including 5,056 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 0.073 (585 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4471 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3	c.1621+109C>A		intron_variant		ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10	c.1621+109C>A		intron_variant		1	NM_006297.3	P1
XRCC1	ENST00000543982.5	c.1528+109C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11058 AN: 152084 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0857

GnomAD4 exome AF: 0.0705 AC: 90460 AN: 1282858 Hom.: 4471 AF XY: 0.0710 AC XY: 45118 AN XY: 635320

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0649

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.0791

GnomAD4 genome AF: 0.0727 AC: 11060 AN: 152202 Hom.: 585 Cov.: 32 AF XY: 0.0732 AC XY: 5448 AN XY: 74416

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0630 Hom.: 44

Bravo AF: 0.0794

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
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: rs25478; hg19: chr19-44049861; COSMIC: COSV53448437;