dbSNP rs1051677: XRCC5:c.*323T>C (chr2-216205525-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021141.4(XRCC5):c.*323T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 335,004 control chromosomes in the GnomAD database, including 3,088 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 0.12 ( 1214 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1874 hom. )

Consequence

XRCC5
NM_021141.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.150

Publications

34 publications found

Variant links:

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

XRCC5 links:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4 link	c.*323T>C		3_prime_UTR_variant	Exon 21 of 21	ENST00000392132.7	NP_066964.1	P13010

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
XRCC5	ENST00000392132.7 link	c.*323T>C	3_prime_UTR_variant	Exon 21 of 21	1	NM_021141.4	ENSP00000375977.2	P13010
XRCC5	ENST00000392133.7 link	c.*323T>C	3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000375978.3	P13010
XRCC5	ENST00000460284.5 link	n.*102T>C	downstream_gene_variant		1
XRCC5	ENST00000485763.1 link	n.*103T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17885

AN:

152076

Hom.:

1214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0834

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.128

AC:

23313

AN:

182810

Hom.:

1874

Cov.:

AF XY:

0.137

AC XY:

13311

AN XY:

97266

show subpopulations

African (AFR)

AF:

0.130

AC:

702

AN:

5408

American (AMR)

AF:

0.0709

AC:

480

AN:

6770

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

674

AN:

5542

East Asian (EAS)

AF:

0.150

AC:

1595

AN:

10652

South Asian (SAS)

AF:

0.269

AC:

5698

AN:

21190

European-Finnish (FIN)

AF:

0.119

AC:

1134

AN:

9542

Middle Eastern (MID)

AF:

0.163

AC:

134

AN:

824

European-Non Finnish (NFE)

AF:

0.103

AC:

11591

AN:

112234

Other (OTH)

AF:

0.123

AC:

1305

AN:

10648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

970

1940

2911

3881

4851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.118

AC:

17901

AN:

152194

Hom.:

1214

Cov.:

AF XY:

0.118

AC XY:

8811

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.129

AC:

5375

AN:

41528

American (AMR)

AF:

0.0833

AC:

1274

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3470

East Asian (EAS)

AF:

0.150

AC:

774

AN:

5176

South Asian (SAS)

AF:

0.277

AC:

1333

AN:

4818

European-Finnish (FIN)

AF:

0.118

AC:

1250

AN:

10596

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.104

AC:

7085

AN:

68002

Other (OTH)

AF:

0.108

AC:

228

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

802

1604

2405

3207

4009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.103

Hom.:

1136

Bravo

AF:

0.111

Asia WGS

AF:

0.205

AC:

713

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

(source)

DANN

Benign

0.58

PhyloP100

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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