12-950115-A-T

Position:

• chr12-950115-A-T

Variant summary

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

The ENST00000430095.6(RAD52):​c.-18-17039T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,038 control chromosomes in the GnomAD database, including 17,885 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 0.48 (17885 hom., cov: 33)
• Consequence: RAD52 ENST00000430095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

RAD52 (HGNC:9824): (RAD52 homolog, DNA repair protein) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_001297419.1	c.-18-17039T>A		intron_variant			NP_001284348.1
RAD52	XM_005253720.6	c.-18-17039T>A		intron_variant			XP_005253777.1
RAD52	XM_017019769.2	c.-18-17039T>A		intron_variant			XP_016875258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000430095.6	c.-18-17039T>A		intron_variant		1		ENSP00000387901	P2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73367 AN: 151920 Hom.: 17878 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.471

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.483 AC: 73406 AN: 152038 Hom.: 17885 Cov.: 33 AF XY: 0.479 AC XY: 35612 AN XY: 74356

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.473

Alfa AF: 0.493 Hom.: 2241

Bravo AF: 0.487

Asia WGS AF: 0.415 AC: 1443 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	2.2
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11571378; hg19: chr12-1059281;