rs25484

Variant names:

• chr19-43546814-T-C
• rs25484
• NM_006297.3:c.1293+70A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006297.3(XRCC1):​c.1293+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,596,984 control chromosomes in the GnomAD database, including 25,306 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 0.16 (2097 hom., cov: 31)
  • Exomes 𝑓: 0.17 (23209 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 14 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.1293+70A>G		intron	N/A	NP_006288.2	P18887

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.1293+70A>G		intron	N/A	ENSP00000262887.5	P18887
	XRCC1	ENST00000953258.1		c.1305+70A>G		intron	N/A	ENSP00000623317.1
	XRCC1	ENST00000865401.1		c.1290+70A>G		intron	N/A	ENSP00000535460.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24744 AN: 151550 Hom.: 2099 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.150 AC: 36308 AN: 242772 AF XY: 0.154

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0916

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.000928

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.174 AC: 251997 AN: 1445316 Hom.: 23209 Cov.: 33 AF XY: 0.174 AC XY: 124849 AN XY: 716316

African (AFR) AF: 0.148 AC: 4909 AN: 33206

American (AMR) AF: 0.0936 AC: 4122 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3346 AN: 25332

East Asian (EAS) AF: 0.000457 AC: 18 AN: 39350

South Asian (SAS) AF: 0.149 AC: 12636 AN: 84972

European-Finnish (FIN) AF: 0.173 AC: 8993 AN: 52016

Middle Eastern (MID) AF: 0.140 AC: 795 AN: 5682

European-Non Finnish (NFE) AF: 0.188 AC: 207431 AN: 1101080

Other (OTH) AF: 0.163 AC: 9747 AN: 59624

GnomAD4 genome AF: 0.163 AC: 24756 AN: 151668 Hom.: 2097 Cov.: 31 AF XY: 0.161 AC XY: 11919 AN XY: 74090

African (AFR) AF: 0.151 AC: 6243 AN: 41334

American (AMR) AF: 0.130 AC: 1986 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3466

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5138

South Asian (SAS) AF: 0.131 AC: 629 AN: 4800

European-Finnish (FIN) AF: 0.177 AC: 1869 AN: 10536

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13002 AN: 67860

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.178 Hom.: 549

Bravo AF: 0.157

Asia WGS AF: 0.0610 AC: 214 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	11
DANN	Benign	0.69
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs25484; hg19: chr19-44050966;