rs1801320

Variant names:

• chr15-40695330-G-C
• rs1801320
• NM_002875.5:c.-98G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 251 publications found

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]

RAD51-AS1 (HGNC:48621): (RAD51 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	NM_002875.5	MANE Select	c.-98G>C		5_prime_UTR	Exon 1 of 10	NP_002866.2
	RAD51	NM_133487.4		c.-98G>C		5_prime_UTR	Exon 1 of 10	NP_597994.3	Q06609-4
	RAD51	NM_001164270.2		c.-98G>C		5_prime_UTR	Exon 1 of 9	NP_001157742.1	Q06609-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	ENST00000267868.8	TSL:1 MANE Select	c.-98G>C		5_prime_UTR	Exon 1 of 10	ENSP00000267868.3	Q06609-1
	RAD51	ENST00000423169.6	TSL:1	c.-98G>C		5_prime_UTR	Exon 1 of 9	ENSP00000406602.2	Q06609-3
	RAD51	ENST00000557850.5	TSL:2	c.-98G>C		5_prime_UTR	Exon 1 of 8	ENSP00000454176.1	Q06609-2

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 1 AN: 8

East Asian (EAS) AF: 0.100 AC: 1 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.0566 AC: 18 AN: 318

Other (OTH) AF: 0.100 AC: 2 AN: 20

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

African (AFR) AF: 0.229 AC: 9503 AN: 41540

American (AMR) AF: 0.0750 AC: 1148 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3472

East Asian (EAS) AF: 0.153 AC: 791 AN: 5176

South Asian (SAS) AF: 0.122 AC: 590 AN: 4830

European-Finnish (FIN) AF: 0.0928 AC: 984 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5091 AN: 68026

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.109 Hom.: 131

Bravo AF: 0.126

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Breast cancer, susceptibility to, in BRCA1 and BRCA2 carriers (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		0.28
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	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: rs1801320; hg19: chr15-40987528;