15-40695527-C-T

Variant names:

• chr15-40695527-C-T
• rs3092981
• ENST00000532743.6:c.-102C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000532743.6(RAD51):​c.-102C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,258 control chromosomes in the GnomAD database, including 780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (779 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: RAD51 ENST00000532743.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.288
• Publications: 15 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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group R

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mirror movements 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-40695527-C-T is Benign according to our data. Variant chr15-40695527-C-T is described in ClinVar as Benign. ClinVar VariationId is 1261176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.-3+102C>T		intron_variant	Intron 1 of 9	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000532743.6	c.-102C>T		5_prime_UTR_variant	Exon 1 of 10	2		ENSP00000433924.2
RAD51	ENST00000267868.8	c.-3+102C>T		intron_variant	Intron 1 of 9	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000557850.5	c.-3+102C>T		intron_variant	Intron 1 of 7	2		ENSP00000454176.1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12593 AN: 152020 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0646

GnomAD4 exome AF: 0.144 AC: 17 AN: 118 Hom.: 1 Cov.: 0 AF XY: 0.174 AC XY: 15 AN XY: 86

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.167 AC: 16 AN: 96

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.0828 AC: 12593 AN: 152140 Hom.: 779 Cov.: 32 AF XY: 0.0823 AC XY: 6123 AN XY: 74398

African (AFR) AF: 0.0200 AC: 830 AN: 41556

American (AMR) AF: 0.0588 AC: 899 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.0460 AC: 220 AN: 4780

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8529 AN: 67988

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.102 Hom.: 1362

Bravo AF: 0.0720

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.79
PhyloP100		0.29
PromoterAI		0.049	Neutral
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: rs3092981; hg19: chr15-40987725;