rs12432197

Variant names:

• chr14-68621468-T-C
• rs12432197
• ENST00000488612.5:c.1037-29313T>C

Variant summary

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

The ENST00000488612.5(RAD51B):​c.1037-29313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,140 control chromosomes in the GnomAD database, including 19,511 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 0.50 (19511 hom., cov: 33)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000306917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321818.2	c.1037-61469T>C		intron_variant	Intron 10 of 10		NP_001308747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.1037-29313T>C		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-61469T>C		intron_variant	Intron 4 of 4	3
RAD51B	ENST00000553595.5	n.614-61469T>C		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75911 AN: 152020 Hom.: 19483 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.499 AC: 75991 AN: 152140 Hom.: 19511 Cov.: 33 AF XY: 0.498 AC XY: 37013 AN XY: 74370

African (AFR) AF: 0.596 AC: 24736 AN: 41488

American (AMR) AF: 0.488 AC: 7466 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1830 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5176

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4816

European-Finnish (FIN) AF: 0.446 AC: 4726 AN: 10586

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31740 AN: 67998

Other (OTH) AF: 0.502 AC: 1060 AN: 2112

Alfa AF: 0.482 Hom.: 54847

Bravo AF: 0.503

Asia WGS AF: 0.412 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12432197; hg19: chr14-69088185; COSMIC: COSV66854278;