rs7307680

Variant names:

• chr12-943322-A-G
• rs7307680
• NM_134424.4:c.-19+6280T>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+6280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,270 control chromosomes in the GnomAD database, including 1,748 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 0.15 (1748 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.-19+6280T>C		intron	N/A	NP_602296.2
	RAD52	NM_001297419.1		c.-18-10246T>C		intron	N/A	NP_001284348.1
	RAD52	NM_001297421.2		c.-46+6280T>C		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.-19+6280T>C		intron	N/A	ENSP00000351284.3
	RAD52	ENST00000430095.6	TSL:1	c.-18-10246T>C		intron	N/A	ENSP00000387901.2
	RAD52	ENST00000461568.5	TSL:1	n.-19+6284T>C		intron	N/A	ENSP00000436008.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22385 AN: 152152 Hom.: 1749 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.147 AC: 22393 AN: 152270 Hom.: 1748 Cov.: 32 AF XY: 0.149 AC XY: 11077 AN XY: 74442

African (AFR) AF: 0.0913 AC: 3796 AN: 41558

American (AMR) AF: 0.110 AC: 1679 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3472

East Asian (EAS) AF: 0.0938 AC: 486 AN: 5182

South Asian (SAS) AF: 0.175 AC: 843 AN: 4826

European-Finnish (FIN) AF: 0.240 AC: 2542 AN: 10600

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12058 AN: 68018

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.160 Hom.: 2824

Bravo AF: 0.134

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		0.83
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: rs7307680; hg19: chr12-1052488;