19-43553946-T-C

Variant names:

• chr19-43553946-T-C
• rs762507
• NM_006297.3:c.415-263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006297.3(XRCC1):​c.415-263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,052 control chromosomes in the GnomAD database, including 30,336 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 0.63 (30336 hom., cov: 33)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 16 publications found

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]

XRCC1 Gene-Disease associations (from GenCC):

• head and neck cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spinocerebellar ataxia, autosomal recessive 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000269177 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.415-263A>G		intron_variant	Intron 4 of 16	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.415-263A>G		intron_variant	Intron 4 of 16	1	NM_006297.3	ENSP00000262887.5

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95282 AN: 151934 Hom.: 30319 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.627 AC: 95352 AN: 152052 Hom.: 30336 Cov.: 33 AF XY: 0.630 AC XY: 46797 AN XY: 74338

African (AFR) AF: 0.667 AC: 27657 AN: 41470

American (AMR) AF: 0.729 AC: 11135 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2357 AN: 3468

East Asian (EAS) AF: 0.887 AC: 4585 AN: 5170

South Asian (SAS) AF: 0.643 AC: 3103 AN: 4826

European-Finnish (FIN) AF: 0.541 AC: 5730 AN: 10584

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38677 AN: 67934

Other (OTH) AF: 0.641 AC: 1353 AN: 2110

Alfa AF: 0.593 Hom.: 13098

Bravo AF: 0.649

Asia WGS AF: 0.751 AC: 2607 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	4.6
DANN	Benign	0.38
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs762507; hg19: chr19-44058098;