14-68722359-C-G

Variant names:

• chr14-68722359-C-G
• rs2043672
• ENST00000488612.5:c.*12-7449C>G

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*12-7449C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 151,850 control chromosomes in the GnomAD database, including 443 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 0.063 (443 hom., cov: 31)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.35
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488612.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.*12-7449C>G		intron	N/A	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9570 AN: 151732 Hom.: 445 Cov.: 31

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0534

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

GnomAD4 genome AF: 0.0630 AC: 9563 AN: 151850 Hom.: 443 Cov.: 31 AF XY: 0.0687 AC XY: 5095 AN XY: 74158

African (AFR) AF: 0.0216 AC: 893 AN: 41426

American (AMR) AF: 0.0446 AC: 681 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3472

East Asian (EAS) AF: 0.178 AC: 912 AN: 5114

South Asian (SAS) AF: 0.132 AC: 637 AN: 4808

European-Finnish (FIN) AF: 0.158 AC: 1657 AN: 10482

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4500 AN: 67972

Other (OTH) AF: 0.0533 AC: 112 AN: 2102

Alfa AF: 0.0302 Hom.: 26

Bravo AF: 0.0514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.51
PhyloP100		-4.4
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: rs2043672; hg19: chr14-69189076;