ENST00000430095.6:c.-18-17039T>A

Variant names:

• chr12-950115-A-T
• rs11571378
• ENST00000430095.6:c.-18-17039T>A

Variant summary

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

The ENST00000430095.6(RAD52):​c.-18-17039T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,038 control chromosomes in the GnomAD database, including 17,885 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 0.48 (17885 hom., cov: 33)
• Consequence: RAD52 ENST00000430095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_001297419.1	c.-18-17039T>A		intron_variant	Intron 1 of 11		NP_001284348.1
RAD52	XM_005253720.6	c.-18-17039T>A		intron_variant	Intron 2 of 12		XP_005253777.1
RAD52	XM_017019769.2	c.-18-17039T>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.-18-17039T>A		intron_variant	Intron 1 of 11	1		ENSP00000387901.2
ENSG00000299067	ENST00000760289.1	n.30A>T		non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000299067	ENST00000760288.1	n.89+389A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73367 AN: 151920 Hom.: 17878 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.483 AC: 73406 AN: 152038 Hom.: 17885 Cov.: 33 AF XY: 0.479 AC XY: 35612 AN XY: 74356

African (AFR) AF: 0.466 AC: 19315 AN: 41476

American (AMR) AF: 0.509 AC: 7774 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1466 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1757 AN: 5148

South Asian (SAS) AF: 0.474 AC: 2285 AN: 4818

European-Finnish (FIN) AF: 0.404 AC: 4283 AN: 10592

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35028 AN: 67946

Other (OTH) AF: 0.473 AC: 997 AN: 2110

Alfa AF: 0.493 Hom.: 2241

Bravo AF: 0.487

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		-1.6
PromoterAI		-0.0010	Neutral
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: rs11571378; hg19: chr12-1059281;