rs3748523

chr12-949572-C-G

Variant summary

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

The NM_134424.4(RAD52):c.-19+30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,440 control chromosomes in the GnomAD database, including 1,222 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 0.12 (1220 hom., cov: 32)
  • Exomes 𝑓: 0.094 (2 hom.)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.-19+30G>C		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.-19+30G>C		intron_variant		1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18541 AN: 151928 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0939 AC: 37 AN: 394 Hom.: 2 Cov.: 0 AF XY: 0.0845 AC XY: 25 AN XY: 296

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.122 AC: 18557 AN: 152046 Hom.: 1220 Cov.: 32 AF XY: 0.126 AC XY: 9388 AN XY: 74326

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.104

Alfa AF: 0.119 Hom.: 150

Bravo AF: 0.111

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.2
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3748523; hg19: chr12-1058738; COSMIC: COSV61922698; COSMIC: COSV61922698;