rs1051685

chr2-216205653-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
XRCC5	NM_021141.4	c.*451A>G		3_prime_UTR_variant	21/21	ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC5	ENST00000392132.7	c.*451A>G		3_prime_UTR_variant	21/21	1	NM_021141.4	P1
XRCC5	ENST00000392133.7	c.*451A>G		3_prime_UTR_variant	23/23	5		P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26550 AN: 151992 Hom.: 2935 Cov.: 32

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.: 30 Cov.: 0 AF XY: 0.122 AC XY: 319 AN XY: 2616

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.175 AC: 26617 AN: 152110 Hom.: 2949 Cov.: 32 AF XY: 0.175 AC XY: 12999 AN XY: 74362

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0721

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.141

Alfa AF: 0.129 Hom.: 2510

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
Dann	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs1051685; hg19: chr2-217070376;