dbSNP rs41296835: XRCC5:c.*301A>G (chr2-216205503-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021141.4(XRCC5):c.*301A>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 0.00472 in 393,412 control chromosomes in the GnomAD database, including 33 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 0.010 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

XRCC5
NM_021141.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Publications

4 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:

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=-0.64).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1571/152306) while in subpopulation AFR AF = 0.0362 (1503/41552). AF 95% confidence interval is 0.0347. There are 27 homozygotes in GnomAd4. There are 746 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4 link	c.*301A>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.*301A>G	3_prime_UTR_variant	Exon 21 of 21	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000392133.7 link	c.*301A>G	3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000375978.3
XRCC5	ENST00000460284.5 link	n.*80A>G	downstream_gene_variant		1
XRCC5	ENST00000485763.1 link	n.*81A>G	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1572

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00118

AC:

284

AN:

241106

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

141

AN XY:

127342

show subpopulations

African (AFR)

AF:

0.0309

AC:

218

AN:

7066

American (AMR)

AF:

0.00183

AC:

AN:

8756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7700

East Asian (EAS)

AF:

0.00

AC:

AN:

15552

South Asian (SAS)

AF:

0.000205

AC:

AN:

24426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13996

Middle Eastern (MID)

AF:

0.00438

AC:

AN:

1142

European-Non Finnish (NFE)

AF:

0.0000608

AC:

AN:

148104

Other (OTH)

AF:

0.00216

AC:

AN:

14364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

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:

0.0103

AC:

1571

AN:

152306

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0362

AC:

1503

AN:

41552

American (AMR)

AF:

0.00327

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68026

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00427

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism

(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