rs3213255

Variant names:

• chr19-43573355-G-A
• rs3213255
• NM_006297.3:c.144+1555C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43573355-G-A
• chr19-43573355-G-C
• chr19-43573355-G-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.144+1555C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,968 control chromosomes in the GnomAD database, including 28,191 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 0.61 (28191 hom., cov: 31)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 36 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.144+1555C>T		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.144+1555C>T		intron_variant	Intron 2 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.169-12335C>T		intron_variant	Intron 1 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91937 AN: 151852 Hom.: 28176 Cov.: 31

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.605 AC: 91993 AN: 151968 Hom.: 28191 Cov.: 31 AF XY: 0.609 AC XY: 45192 AN XY: 74260

African (AFR) AF: 0.590 AC: 24456 AN: 41418

American (AMR) AF: 0.700 AC: 10689 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2276 AN: 3466

East Asian (EAS) AF: 0.880 AC: 4547 AN: 5168

South Asian (SAS) AF: 0.627 AC: 3019 AN: 4816

European-Finnish (FIN) AF: 0.557 AC: 5876 AN: 10540

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39113 AN: 67966

Other (OTH) AF: 0.614 AC: 1297 AN: 2112

Alfa AF: 0.586 Hom.: 21348

Bravo AF: 0.621

Asia WGS AF: 0.732 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.013
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: rs3213255; hg19: chr19-44077507;