rs12470053

chr2-216190448-A-Gchr2-216190448-A-T

Variant summary

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

The NM_021141.4(XRCC5):c.1944+114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 854,146 control chromosomes in the GnomAD database, including 194,950 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 0.72 (41448 hom., cov: 32)
  • Exomes 𝑓: 0.65 (153502 hom.)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4	c.1944+114A>G		intron_variant		ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC5	ENST00000392132.7	c.1944+114A>G		intron_variant		1	NM_021141.4	P1
XRCC5	ENST00000460284.5	n.2486+114A>G		intron_variant, non_coding_transcript_variant		1
XRCC5	ENST00000392133.7	c.1944+114A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110111 AN: 152042 Hom.: 41382 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.651 AC: 457144 AN: 701986 Hom.: 153502 AF XY: 0.654 AC XY: 237433 AN XY: 362806

Gnomad4 AFR exome AF: 0.915

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.724 AC: 110235 AN: 152160 Hom.: 41448 Cov.: 32 AF XY: 0.731 AC XY: 54372 AN XY: 74374

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.716

Alfa AF: 0.666 Hom.: 4995

Bravo AF: 0.741

Asia WGS AF: 0.847 AC: 2946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.22
Dann	Benign	0.33

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: rs12470053; hg19: chr2-217055171;