14-67832095-G-T

Variant names:

• chr14-67832095-G-T
• rs11626809
• NM_133510.4:c.199-2985G>T

Variant summary

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

The NM_133510.4(RAD51B):​c.199-2985G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,276 control chromosomes in the GnomAD database, including 982 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 0.097 (982 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.199-2985G>T		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.199-2985G>T		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.199-2985G>T		intron	N/A	NP_598193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.199-2985G>T		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.199-2985G>T		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.199-2985G>T		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14840 AN: 152158 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.0974 AC: 14828 AN: 152276 Hom.: 982 Cov.: 32 AF XY: 0.0974 AC XY: 7250 AN XY: 74454

African (AFR) AF: 0.0244 AC: 1015 AN: 41560

American (AMR) AF: 0.112 AC: 1709 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.00616 AC: 32 AN: 5194

South Asian (SAS) AF: 0.158 AC: 761 AN: 4826

European-Finnish (FIN) AF: 0.0959 AC: 1016 AN: 10596

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9032 AN: 68018

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.113 Hom.: 566

Bravo AF: 0.0963

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.43
PhyloP100		-0.57
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: rs11626809; hg19: chr14-68298812;