rs1833095

Variant names:

• chr12-937042-C-T
• rs1833095
• NM_134424.4:c.-18-3966G>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.-18-3966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,018 control chromosomes in the GnomAD database, including 39,675 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 0.72 (39675 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-18-3966G>A		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.-18-3966G>A		intron_variant	Intron 1 of 11	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109266 AN: 151900 Hom.: 39653 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.719 AC: 109336 AN: 152018 Hom.: 39675 Cov.: 32 AF XY: 0.721 AC XY: 53539 AN XY: 74294

African (AFR) AF: 0.636 AC: 26377 AN: 41454

American (AMR) AF: 0.705 AC: 10764 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2593 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3269 AN: 5154

South Asian (SAS) AF: 0.852 AC: 4113 AN: 4826

European-Finnish (FIN) AF: 0.761 AC: 8040 AN: 10560

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51853 AN: 67960

Other (OTH) AF: 0.723 AC: 1529 AN: 2114

Alfa AF: 0.741 Hom.: 5204

Bravo AF: 0.707

Asia WGS AF: 0.743 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.35
PhyloP100		-0.51
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: rs1833095; hg19: chr12-1046208;