rs1833095

Positions:

• chr12-937042-C-T

Variant summary

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

The NM_134424.4(RAD52):​c.-18-3966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,018 control chromosomes in the GnomAD database, including 39,675 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 (39675 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-18-3966G>A		intron_variant		ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.-18-3966G>A		intron_variant		1	NM_134424.4	ENSP00000351284	P2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109266 AN: 151900 Hom.: 39653 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.719 AC: 109336 AN: 152018 Hom.: 39675 Cov.: 32 AF XY: 0.721 AC XY: 53539 AN XY: 74294

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.723

Alfa AF: 0.741 Hom.: 5204

Bravo AF: 0.707

Asia WGS AF: 0.743 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.35

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: rs1833095; hg19: chr12-1046208;