dbSNP rs25484: XRCC1:c.1293+70A>G (chr19-43546814-T-C) – ACMG Classification: Benign (-8 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.778

Publications

13 publications found

Variant links:

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)

XRCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.1293+70A>G		intron_variant	Intron 11 of 16	ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 link	c.1293+70A>G		intron_variant	Intron 11 of 16	1	NM_006297.3	ENSP00000262887.5		P18887
XRCC1	ENST00000543982.5 link	c.1200+70A>G		intron_variant	Intron 10 of 15	2		ENSP00000443671.1		F5H8D7

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24744

AN:

151550

Hom.:

2099

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.174

AC XY:

124849

AN XY:

716316

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

12028

24056

36084

48112

60140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7212

14424

21636

28848

36060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24756

AN:

151668

Hom.:

2097

Cov.:

AF XY:

0.161

AC XY:

11919

AN XY:

74090

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.192

AC:

13002

AN:

67860

Other (OTH)

AF:

0.153

AC:

324

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1034

2067

3101

4134

5168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over