Genetic Variant XRCC1:c.415-213C>T (chr19-43553896-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.415-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 483,326 control chromosomes in the GnomAD database, including 2,669 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 0.073 ( 624 hom., cov: 32)

Exomes 𝑓: 0.085 ( 2045 hom. )

Consequence

XRCC1
NM_006297.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Publications

14 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC1	NM_006297.3 link	c.415-213C>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.415-213C>T		intron_variant	Intron 4 of 16	1	NM_006297.3	ENSP00000262887.5		P18887

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11128

AN:

152100

Hom.:

624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0620

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0613

Gnomad OTH

AF:

0.0852

GnomAD4 exome

AF:

0.0852

AC:

28198

AN:

331108

Hom.:

2045

AF XY:

0.0851

AC XY:

14344

AN XY:

168600

show subpopulations

African (AFR)

AF:

0.0641

AC:

703

AN:

10974

American (AMR)

AF:

0.118

AC:

1573

AN:

13378

Ashkenazi Jewish (ASJ)

AF:

0.0633

AC:

692

AN:

10930

East Asian (EAS)

AF:

0.305

AC:

8623

AN:

28244

South Asian (SAS)

AF:

0.0918

AC:

1242

AN:

13524

European-Finnish (FIN)

AF:

0.0362

AC:

1143

AN:

31532

Middle Eastern (MID)

AF:

0.0856

AC:

131

AN:

1530

European-Non Finnish (NFE)

AF:

0.0618

AC:

12413

AN:

200792

Other (OTH)

AF:

0.0831

AC:

1678

AN:

20204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1158

2316

3475

4633

5791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.0731

AC:

11130

AN:

152218

Hom.:

624

Cov.:

AF XY:

0.0738

AC XY:

5491

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0620

AC:

2575

AN:

41522

American (AMR)

AF:

0.101

AC:

1551

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0591

AC:

205

AN:

3470

East Asian (EAS)

AF:

0.292

AC:

1512

AN:

5178

South Asian (SAS)

AF:

0.103

AC:

496

AN:

4828

European-Finnish (FIN)

AF:

0.0369

AC:

392

AN:

10614

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0613

AC:

4171

AN:

68002

Other (OTH)

AF:

0.0853

AC:

180

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

511

1022

1533

2044

2555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0665

Hom.:

Bravo

AF:

0.0798

Asia WGS

AF:

0.189

AC:

656

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.8

(source)

DANN

Benign

0.53

PhyloP100

1.3

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

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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