14-68350696-T-C

Variant names:

• chr14-68350696-T-C
• rs8009876
• NM_133510.4:c.853+58716T>C

Variant summary

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

The NM_133510.4(RAD51B):​c.853+58716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,290 control chromosomes in the GnomAD database, including 59,171 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 0.88 (59171 hom., cov: 33)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.853+58716T>C		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.853+58716T>C		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.853+58716T>C		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.853+58716T>C		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.853+58716T>C		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.853+58716T>C		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133791 AN: 152172 Hom.: 59101 Cov.: 33

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.879 AC: 133921 AN: 152290 Hom.: 59171 Cov.: 33 AF XY: 0.877 AC XY: 65327 AN XY: 74454

African (AFR) AF: 0.960 AC: 39909 AN: 41572

American (AMR) AF: 0.867 AC: 13262 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5165 AN: 5192

South Asian (SAS) AF: 0.806 AC: 3888 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8987 AN: 10598

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57250 AN: 68018

Other (OTH) AF: 0.848 AC: 1788 AN: 2108

Alfa AF: 0.847 Hom.: 105913

Bravo AF: 0.886

Asia WGS AF: 0.904 AC: 3146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		0.62
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: rs8009876; hg19: chr14-68817413;