chr19-43571484-G-A

Variant names:

• chr19-43571484-G-A
• rs3213266
• NM_006297.3:c.144+3426C>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+3426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,162 control chromosomes in the GnomAD database, including 960 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 0.10 (960 hom., cov: 33)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 17 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 (AMR) allele frequency at 95% confidence interval = 0.15 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.144+3426C>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.144+3426C>T		intron	N/A	ENSP00000262887.5
	ENSG00000268361	ENST00000594374.1	TSL:3	c.169-10464C>T		intron	N/A	ENSP00000472698.1
	XRCC1	ENST00000543982.5	TSL:2	c.51+3924C>T		intron	N/A	ENSP00000443671.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15661 AN: 152044 Hom.: 956 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0988

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

GnomAD4 genome AF: 0.103 AC: 15664 AN: 152162 Hom.: 960 Cov.: 33 AF XY: 0.105 AC XY: 7777 AN XY: 74374

African (AFR) AF: 0.117 AC: 4845 AN: 41516

American (AMR) AF: 0.155 AC: 2375 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5184

South Asian (SAS) AF: 0.0461 AC: 222 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10574

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5862 AN: 67998

Other (OTH) AF: 0.0977 AC: 206 AN: 2108

Alfa AF: 0.0938 Hom.: 448

Bravo AF: 0.110

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.68
PhyloP100		-0.61
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: rs3213266; hg19: chr19-44075636;