dbSNP rs731420: XRCC1:c.415-137C>T (chr19-43553820-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006297.3(XRCC1):c.415-137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 663,654 control chromosomes in the GnomAD database, including 793 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 0.054 ( 311 hom., cov: 31)

Exomes 𝑓: 0.037 ( 482 hom. )

Consequence

XRCC1
NM_006297.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.693

Publications

11 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:

ENSG00000269177 (HGNC:):

ENSG00000269177 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.415-137C>T		intron_variant	Intron 4 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.415-137C>T		intron_variant	Intron 4 of 16	1	NM_006297.3	ENSP00000262887.5		P18887

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8269

AN:

152074

Hom.:

309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.0292

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0550

GnomAD4 exome

AF:

0.0368

AC:

18800

AN:

511460

Hom.:

482

Cov.:

AF XY:

0.0357

AC XY:

9366

AN XY:

262088

show subpopulations

African (AFR)

AF:

0.105

AC:

1456

AN:

13816

American (AMR)

AF:

0.0363

AC:

676

AN:

18598

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

767

AN:

13450

East Asian (EAS)

AF:

0.106

AC:

3353

AN:

31682

South Asian (SAS)

AF:

0.0246

AC:

922

AN:

37490

European-Finnish (FIN)

AF:

0.0329

AC:

1411

AN:

42828

Middle Eastern (MID)

AF:

0.0431

AC:

AN:

2044

European-Non Finnish (NFE)

AF:

0.0275

AC:

8923

AN:

324086

Other (OTH)

AF:

0.0438

AC:

1204

AN:

27466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

960

1920

2879

3839

4799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0544

AC:

8284

AN:

152194

Hom.:

311

Cov.:

AF XY:

0.0544

AC XY:

4050

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.105

AC:

4372

AN:

41472

American (AMR)

AF:

0.0403

AC:

616

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

198

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

564

AN:

5166

South Asian (SAS)

AF:

0.0342

AC:

165

AN:

4826

European-Finnish (FIN)

AF:

0.0292

AC:

310

AN:

10624

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0267

AC:

1817

AN:

68016

Other (OTH)

AF:

0.0563

AC:

119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

398

796

1193

1591

1989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0389

Hom.:

Bravo

AF:

0.0591

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.0

(source)

DANN

Benign

0.35

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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