Genetic Variant XRCC5:c.*727C>A (chr2-216205929-C-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_021141.4(XRCC5):c.*727C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,134 control chromosomes in the GnomAD database, including 1,207 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 ( 1207 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

XRCC5
NM_021141.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

15 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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.*727C>A		3_prime_UTR	Exon 21 of 21	NP_066964.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.*727C>A	3_prime_UTR	Exon 21 of 21	ENSP00000375977.2
XRCC5	ENST00000947464.1		c.*727C>A	3_prime_UTR	Exon 22 of 22	ENSP00000617523.1
XRCC5	ENST00000947463.1		c.*727C>A	3_prime_UTR	Exon 21 of 21	ENSP00000617522.1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17835

AN:

152014

Hom.:

1207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0834

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.117

AC:

17851

AN:

152132

Hom.:

1207

Cov.:

AF XY:

0.118

AC XY:

8778

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.129

AC:

5339

AN:

41488

American (AMR)

AF:

0.0833

AC:

1273

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

404

AN:

3468

East Asian (EAS)

AF:

0.150

AC:

775

AN:

5182

South Asian (SAS)

AF:

0.276

AC:

1326

AN:

4810

European-Finnish (FIN)

AF:

0.118

AC:

1245

AN:

10592

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7085

AN:

67998

Other (OTH)

AF:

0.107

AC:

227

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

788

1576

2363

3151

3939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.104

Hom.:

1108

Bravo

AF:

0.111

Asia WGS

AF:

0.205

AC:

711

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.20

(source)

DANN

Benign

0.68

PhyloP100

-2.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over