12-946286-A-G

Variant names:

• chr12-946286-A-G
• rs11064607
• NM_134424.4:c.-19+3316T>C

Variant summary

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

The NM_134424.4(RAD52):​c.-19+3316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,964 control chromosomes in the GnomAD database, including 15,117 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 0.44 (15117 hom., cov: 31)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-19+3316T>C		intron_variant	Intron 1 of 11	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.-19+3316T>C		intron_variant	Intron 1 of 11	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67570 AN: 151846 Hom.: 15113 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.445 AC: 67610 AN: 151964 Hom.: 15117 Cov.: 31 AF XY: 0.443 AC XY: 32907 AN XY: 74266

African (AFR) AF: 0.442 AC: 18343 AN: 41460

American (AMR) AF: 0.472 AC: 7197 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1736 AN: 5160

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4820

European-Finnish (FIN) AF: 0.384 AC: 4049 AN: 10540

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31293 AN: 67942

Other (OTH) AF: 0.449 AC: 947 AN: 2110

Alfa AF: 0.457 Hom.: 22672

Bravo AF: 0.450

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.3
DANN	Benign	0.81
PhyloP100		0.71
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: rs11064607; hg19: chr12-1055452;