rs11571461

Variant names:

• chr12-917153-T-C
• rs11571461
• NM_134424.4:c.544-333A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.544-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 152,214 control chromosomes in the GnomAD database, including 442 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 0.070 (442 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.544-333A>G		intron_variant	Intron 7 of 11	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.544-333A>G		intron_variant	Intron 7 of 11	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10638 AN: 152096 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0700 AC: 10655 AN: 152214 Hom.: 442 Cov.: 32 AF XY: 0.0692 AC XY: 5152 AN XY: 74422

African (AFR) AF: 0.0860 AC: 3573 AN: 41548

American (AMR) AF: 0.0652 AC: 997 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4818

European-Finnish (FIN) AF: 0.0751 AC: 795 AN: 10590

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4559 AN: 68008

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0721 Hom.: 49

Bravo AF: 0.0716

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.46
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11571461; hg19: chr12-1026319;