rs3815855

Positions:

• chr2-216117647-C-G
• chr2-216117647-C-T

Variant summary

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

The NM_021141.4(XRCC5):​c.320-99C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,203,820 control chromosomes in the GnomAD database, including 24,822 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 0.19 (2903 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21919 hom.)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4	c.320-99C>G		intron_variant		ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC5	ENST00000392132.7	c.320-99C>G		intron_variant		1	NM_021141.4	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29580 AN: 152006 Hom.: 2901 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.201 AC: 211727 AN: 1051696 Hom.: 21919 Cov.: 13 AF XY: 0.200 AC XY: 107170 AN XY: 536730

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.195 AC: 29592 AN: 152124 Hom.: 2903 Cov.: 32 AF XY: 0.197 AC XY: 14643 AN XY: 74354

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.198

Alfa AF: 0.198 Hom.: 381

Bravo AF: 0.192

Asia WGS AF: 0.143 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3815855; hg19: chr2-216982370; COSMIC: COSV67536994; COSMIC: COSV67536994;