chr19-43564041-C-T

Variant names:

• chr19-43564041-C-T
• rs2854496
• NM_006297.3:c.145-3021G>A

Variant summary

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

The NM_006297.3(XRCC1):​c.145-3021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,122 control chromosomes in the GnomAD database, including 2,055 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 0.16 (2055 hom., cov: 32)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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]

ENSG00000268361 (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 = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.145-3021G>A		intron_variant	Intron 2 of 16	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.145-3021G>A		intron_variant	Intron 2 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.169-3021G>A		intron_variant	Intron 1 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24459 AN: 152004 Hom.: 2057 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.161 AC: 24471 AN: 152122 Hom.: 2055 Cov.: 32 AF XY: 0.158 AC XY: 11766 AN XY: 74344

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.155

Alfa AF: 0.180 Hom.: 5078

Bravo AF: 0.155

Asia WGS AF: 0.0610 AC: 215 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	4.0
DANN	Benign	0.86

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: rs2854496; hg19: chr19-44068193;