dbSNP rs1051685: XRCC5:c.*451A>G (chr2-216205653-A-G) – 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.*451A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 157,042 control chromosomes in the GnomAD database, including 2,979 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 0.17 ( 2949 hom., cov: 32)

Exomes 𝑓: 0.11 ( 30 hom. )

Consequence

XRCC5
NM_021141.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.41

Publications

40 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4 link	c.*451A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
XRCC5	ENST00000392132.7 link	c.*451A>G	3_prime_UTR_variant	Exon 21 of 21	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000392133.7 link	c.*451A>G	3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000375978.3
XRCC5	ENST00000460284.5 link	n.*230A>G	downstream_gene_variant		1
XRCC5	ENST00000485763.1 link	n.*231A>G	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26550

AN:

151992

Hom.:

2935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.112

AC:

554

AN:

4932

Hom.:

Cov.:

AF XY:

0.122

AC XY:

319

AN XY:

2616

show subpopulations

African (AFR)

AF:

0.351

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

498

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

AN:

112

East Asian (EAS)

AF:

0.0671

AC:

AN:

164

South Asian (SAS)

AF:

0.156

AC:

AN:

422

European-Finnish (FIN)

AF:

0.128

AC:

AN:

156

Middle Eastern (MID)

AF:

0.111

AC:

AN:

European-Non Finnish (NFE)

AF:

0.104

AC:

342

AN:

3292

Other (OTH)

AF:

0.122

AC:

AN:

196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.175

AC:

26617

AN:

152110

Hom.:

2949

Cov.:

AF XY:

0.175

AC XY:

12999

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.319

AC:

13225

AN:

41442

American (AMR)

AF:

0.120

AC:

1832

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

476

AN:

3470

East Asian (EAS)

AF:

0.0721

AC:

374

AN:

5190

South Asian (SAS)

AF:

0.174

AC:

837

AN:

4824

European-Finnish (FIN)

AF:

0.113

AC:

1202

AN:

10594

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8285

AN:

68000

Other (OTH)

AF:

0.141

AC:

297

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1046

2091

3137

4182

5228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.136

Hom.:

6570

Bravo

AF:

0.180

Asia WGS

AF:

0.143

AC:

498

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0070

(source)

DANN

Benign

0.30

PhyloP100

-4.4

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