rs11571476

chr12-912992-T-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_134424.4(RAD52):c.*398_*399insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 224,158 control chromosomes in the GnomAD database, including 21,158 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14304 hom., cov: 0)
  • Exomes 𝑓: 0.43 (6854 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.*398_*399insT		3_prime_UTR_variant	12/12	ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.*398_*399insT		3_prime_UTR_variant	12/12	1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65096 AN: 151760 Hom.: 14286 Cov.: 0

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.429 AC: 31026 AN: 72280 Hom.: 6854 Cov.: 0 AF XY: 0.424 AC XY: 14369 AN XY: 33862

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.429 AC: 65146 AN: 151878 Hom.: 14304 Cov.: 0 AF XY: 0.429 AC XY: 31872 AN XY: 74210

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.407

Alfa AF: 0.445 Hom.: 1850

Bravo AF: 0.434

Asia WGS AF: 0.409 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11571476; hg19: chr12-1022158;