rs3213368

Variant names:

• chr19-43551492-G-A
• rs3213368
• NM_006297.3:c.1199+79C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43551492-G-A
• chr19-43551492-G-C

Variant summary

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

The NM_006297.3(XRCC1):​c.1199+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,268,608 control chromosomes in the GnomAD database, including 4,501 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 0.089 (770 hom., cov: 33)
  • Exomes 𝑓: 0.073 (3731 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 9 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.1199+79C>T		intron	N/A	NP_006288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.1199+79C>T		intron	N/A	ENSP00000262887.5
	XRCC1	ENST00000543982.5	TSL:2	c.1106+79C>T		intron	N/A	ENSP00000443671.1
	XRCC1	ENST00000597811.5	TSL:5	n.*392C>T		downstream_gene	N/A	ENSP00000470391.1

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13503 AN: 152090 Hom.: 766 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0841

GnomAD4 exome AF: 0.0728 AC: 81230 AN: 1116400 Hom.: 3731 AF XY: 0.0709 AC XY: 40337 AN XY: 568800

African (AFR) AF: 0.107 AC: 2851 AN: 26562

American (AMR) AF: 0.210 AC: 9013 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 1433 AN: 22714

East Asian (EAS) AF: 0.134 AC: 5094 AN: 37938

South Asian (SAS) AF: 0.0494 AC: 3799 AN: 76950

European-Finnish (FIN) AF: 0.0917 AC: 4372 AN: 47680

Middle Eastern (MID) AF: 0.101 AC: 513 AN: 5070

European-Non Finnish (NFE) AF: 0.0625 AC: 50472 AN: 807670

Other (OTH) AF: 0.0752 AC: 3683 AN: 48946

GnomAD4 genome AF: 0.0888 AC: 13509 AN: 152208 Hom.: 770 Cov.: 33 AF XY: 0.0907 AC XY: 6747 AN XY: 74418

African (AFR) AF: 0.112 AC: 4661 AN: 41522

American (AMR) AF: 0.144 AC: 2204 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.118 AC: 607 AN: 5164

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4826

European-Finnish (FIN) AF: 0.0982 AC: 1042 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4364 AN: 68018

Other (OTH) AF: 0.0833 AC: 176 AN: 2114

Alfa AF: 0.0755 Hom.: 65

Bravo AF: 0.0957

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		0.71
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: rs3213368; hg19: chr19-44055644; COSMIC: COSV53452431; COSMIC: COSV53452431;