rs3213334

Variant names:

• chr19-43558367-A-G
• rs3213334
• NM_006297.3:c.255+2543T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-43558367-A-G
• chr19-43558367-A-T

Variant summary

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

The NM_006297.3(XRCC1):​c.255+2543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 151,934 control chromosomes in the GnomAD database, including 47,544 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 0.79 (47544 hom., cov: 30)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 11 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)

ENSG00000268361 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.255+2543T>C		intron_variant	Intron 3 of 16	ENST00000262887.10	NP_006288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10	c.255+2543T>C		intron_variant	Intron 3 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.279+2543T>C		intron_variant	Intron 2 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119926 AN: 151818 Hom.: 47521 Cov.: 30

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.790 AC: 120009 AN: 151934 Hom.: 47544 Cov.: 30 AF XY: 0.790 AC XY: 58671 AN XY: 74268

African (AFR) AF: 0.818 AC: 33885 AN: 41420

American (AMR) AF: 0.859 AC: 13087 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2797 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4582 AN: 5162

South Asian (SAS) AF: 0.771 AC: 3717 AN: 4818

European-Finnish (FIN) AF: 0.718 AC: 7560 AN: 10536

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51696 AN: 67980

Other (OTH) AF: 0.795 AC: 1674 AN: 2106

Alfa AF: 0.779 Hom.: 6600

Bravo AF: 0.806

Asia WGS AF: 0.812 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		-1.3
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: rs3213334; hg19: chr19-44062519;