rs2023614

Variant names:

• chr19-43560713-C-G
• rs2023614
• NM_006297.3:c.255+197G>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.255+197G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 152,242 control chromosomes in the GnomAD database, including 607 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 0.074 (607 hom., cov: 32)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3	c.255+197G>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+197G>C		intron_variant	Intron 3 of 16	1	NM_006297.3	ENSP00000262887.5
ENSG00000268361	ENST00000594374.1	c.279+197G>C		intron_variant	Intron 2 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11306 AN: 152124 Hom.: 603 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0788

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

GnomAD4 genome AF: 0.0743 AC: 11311 AN: 152242 Hom.: 607 Cov.: 32 AF XY: 0.0770 AC XY: 5731 AN XY: 74436

African (AFR) AF: 0.0254 AC: 1056 AN: 41562

American (AMR) AF: 0.144 AC: 2199 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3472

East Asian (EAS) AF: 0.109 AC: 565 AN: 5166

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5516 AN: 68012

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0770 Hom.: 81

Bravo AF: 0.0781

Asia WGS AF: 0.0860 AC: 298 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	0.99
DANN	Benign	0.78
PhyloP100		-0.53
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: rs2023614; hg19: chr19-44064865; COSMIC: COSV53453923;