rs1801320

Positions:

• chr15-40695330-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002875.5(RAD51):​c.-98G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,656 control chromosomes in the GnomAD database, including 1,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1476 hom., cov: 33)
  • Exomes 𝑓: 0.067 (2 hom.)
• Consequence: RAD51 NM_002875.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.280

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-40695330-G-C is Benign according to our data. Variant chr15-40695330-G-C is described in ClinVar as [Benign]. Clinvar id is 13128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51	NM_002875.5	c.-98G>C		5_prime_UTR_variant	1/10	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.-98G>C		5_prime_UTR_variant	1/10	1	NM_002875.5	ENSP00000267868	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18610 AN: 152148 Hom.: 1456 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0667 AC: 26 AN: 390 Hom.: 2 Cov.: 0 AF XY: 0.0686 AC XY: 21 AN XY: 306

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0566

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.123 AC: 18675 AN: 152266 Hom.: 1476 Cov.: 33 AF XY: 0.123 AC XY: 9126 AN XY: 74454

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.103

Alfa AF: 0.109 Hom.: 131

Bravo AF: 0.126

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	This variant is associated with the following publications: (PMID: 26117002, 22487057, 24930116, 24604328, 23161237, 11248061, 19606696, 24040396, 21647442, 24859942, 22611952, 16398215, 11535547, 21708019, 20640595, 20623332, 20454923, 20396943, 17999359) -

Breast cancer, susceptibility to, in BRCA1 and BRCA2 carriers Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.1
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801320; hg19: chr15-40987528;