chr12-915428-G-T

Variant names:

• chr12-915428-G-T
• rs10744729
• NM_134424.4:c.866-896C>A

Variant summary

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

The NM_134424.4(RAD52):​c.866-896C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,090 control chromosomes in the GnomAD database, including 14,035 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 0.42 (14035 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.866-896C>A		intron	N/A	NP_602296.2	Q5DR82
	RAD52	NM_001297419.1		c.866-896C>A		intron	N/A	NP_001284348.1	Q5DR82
	RAD52	NM_001297421.2		c.635-896C>A		intron	N/A	NP_001284350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.866-896C>A		intron	N/A	ENSP00000351284.3	P43351-1
	RAD52	ENST00000430095.6	TSL:1	c.866-896C>A		intron	N/A	ENSP00000387901.2	P43351-1
	RAD52	ENST00000461568.5	TSL:1	n.*704-896C>A		intron	N/A	ENSP00000436008.1	P43351-3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64482 AN: 151972 Hom.: 14017 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.424 AC: 64530 AN: 152090 Hom.: 14035 Cov.: 32 AF XY: 0.426 AC XY: 31636 AN XY: 74350

African (AFR) AF: 0.348 AC: 14447 AN: 41508

American (AMR) AF: 0.512 AC: 7810 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2729 AN: 5168

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4816

European-Finnish (FIN) AF: 0.441 AC: 4666 AN: 10572

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30442 AN: 67974

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.433 Hom.: 44519

Bravo AF: 0.429

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.57
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10744729; hg19: chr12-1024594;