rs1001581

Variant names:

• chr19-43561236-C-T
• rs1001581
• NM_006297.3:c.145-216G>A

Variant summary

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

The NM_006297.3(XRCC1):​c.145-216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,072 control chromosomes in the GnomAD database, including 10,745 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 0.38 (10745 hom., cov: 32)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 33 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.145-216G>A		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.145-216G>A		intron_variant	Intron 2 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.169-216G>A		intron_variant	Intron 1 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57256 AN: 151954 Hom.: 10732 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.377 AC: 57302 AN: 152072 Hom.: 10745 Cov.: 32 AF XY: 0.373 AC XY: 27750 AN XY: 74354

African (AFR) AF: 0.362 AC: 14990 AN: 41458

American (AMR) AF: 0.362 AC: 5527 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1570 AN: 3466

East Asian (EAS) AF: 0.376 AC: 1948 AN: 5176

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4824

European-Finnish (FIN) AF: 0.338 AC: 3583 AN: 10596

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26486 AN: 67970

Other (OTH) AF: 0.369 AC: 781 AN: 2114

Alfa AF: 0.384 Hom.: 17701

Bravo AF: 0.377

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		-0.18
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: rs1001581; hg19: chr19-44065388;