12-951120-A-T

Variant names:

• chr12-951120-A-T
• rs10774474
• ENST00000430095.6:c.-18-18044T>A

Variant summary

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

The ENST00000430095.6(RAD52):​c.-18-18044T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 145,536 control chromosomes in the GnomAD database, including 39,426 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 0.74 (39426 hom., cov: 28)
• Consequence: RAD52 ENST00000430095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• 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]

ENSG00000299067 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_001297419.1	c.-18-18044T>A		intron_variant	Intron 1 of 11		NP_001284348.1
RAD52	XM_005253720.6	c.-18-18044T>A		intron_variant	Intron 2 of 12		XP_005253777.1
RAD52	XM_017019769.2	c.-18-18044T>A		intron_variant	Intron 2 of 12		XP_016875258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000430095.6	c.-18-18044T>A		intron_variant	Intron 1 of 11	1		ENSP00000387901.2
ENSG00000299067	ENST00000760288.1	n.89+1394A>T		intron_variant	Intron 1 of 2
ENSG00000299067	ENST00000760289.1	n.133+902A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.739 AC: 107516 AN: 145420 Hom.: 39408 Cov.: 28

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.739 AC: 107584 AN: 145536 Hom.: 39426 Cov.: 28 AF XY: 0.738 AC XY: 52364 AN XY: 70936

African (AFR) AF: 0.613 AC: 22442 AN: 36632

American (AMR) AF: 0.716 AC: 10718 AN: 14972

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2440 AN: 3438

East Asian (EAS) AF: 0.631 AC: 3246 AN: 5142

South Asian (SAS) AF: 0.791 AC: 3681 AN: 4656

European-Finnish (FIN) AF: 0.802 AC: 8137 AN: 10140

Middle Eastern (MID) AF: 0.775 AC: 220 AN: 284

European-Non Finnish (NFE) AF: 0.810 AC: 54540 AN: 67328

Other (OTH) AF: 0.726 AC: 1482 AN: 2040

Alfa AF: 0.701 Hom.: 2193

Bravo AF: 0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.15
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10774474; hg19: chr12-1060286;