rs11571424

Variant names:

• chr12-929688-C-T
• rs11571424
• NM_134424.4:c.348+131G>A

Variant summary

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

The ENST00000358495.8(RAD52):​c.348+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 883,670 control chromosomes in the GnomAD database, including 6,174 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 0.094 (789 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5385 hom.)
• Consequence: RAD52 ENST00000358495.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358495.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.348+131G>A		intron	N/A	NP_602296.2
	RAD52	NM_001297419.1		c.348+131G>A		intron	N/A	NP_001284348.1
	RAD52	NM_001297421.2		c.117+131G>A		intron	N/A	NP_001284350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.348+131G>A		intron	N/A	ENSP00000351284.3
	RAD52	ENST00000430095.6	TSL:1	c.348+131G>A		intron	N/A	ENSP00000387901.2
	RAD52	ENST00000545564.5	TSL:1	c.348+131G>A		intron	N/A	ENSP00000440268.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14258 AN: 152040 Hom.: 789 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.106 AC: 26456 AN: 250284 AF XY: 0.112

Gnomad AFR exome AF: 0.0396

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0801

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.116 AC: 84610 AN: 731512 Hom.: 5385 Cov.: 9 AF XY: 0.119 AC XY: 46782 AN XY: 391778

African (AFR) AF: 0.0404 AC: 790 AN: 19572

American (AMR) AF: 0.0543 AC: 2382 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2358 AN: 21658

East Asian (EAS) AF: 0.0993 AC: 3624 AN: 36498

South Asian (SAS) AF: 0.156 AC: 11099 AN: 71176

European-Finnish (FIN) AF: 0.0919 AC: 4848 AN: 52746

Middle Eastern (MID) AF: 0.148 AC: 647 AN: 4376

European-Non Finnish (NFE) AF: 0.123 AC: 54890 AN: 445168

Other (OTH) AF: 0.109 AC: 3972 AN: 36484

GnomAD4 genome AF: 0.0937 AC: 14262 AN: 152158 Hom.: 789 Cov.: 32 AF XY: 0.0931 AC XY: 6923 AN XY: 74380

African (AFR) AF: 0.0411 AC: 1707 AN: 41534

American (AMR) AF: 0.0802 AC: 1225 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.0898 AC: 466 AN: 5188

South Asian (SAS) AF: 0.150 AC: 721 AN: 4818

European-Finnish (FIN) AF: 0.0923 AC: 976 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8416 AN: 68000

Other (OTH) AF: 0.103 AC: 217 AN: 2106

Alfa AF: 0.114 Hom.: 704

Bravo AF: 0.0889

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
DANN	Benign	0.48
PhyloP100		-2.1
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: rs11571424; hg19: chr12-1038854; COSMIC: COSV57272296; COSMIC: COSV57272296;