chr14-68438971-A-G

Variant names:

• chr14-68438971-A-G
• rs4902587
• NM_133510.4:c.957+27444A>G

Variant summary

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

The NM_133510.4(RAD51B):​c.957+27444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,078 control chromosomes in the GnomAD database, including 55,348 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 0.85 (55348 hom., cov: 30)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 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.957+27444A>G		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.957+27444A>G		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.957+27444A>G		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.957+27444A>G		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.957+27444A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.957+27444A>G		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129271 AN: 151960 Hom.: 55280 Cov.: 30

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.851 AC: 129401 AN: 152078 Hom.: 55348 Cov.: 30 AF XY: 0.851 AC XY: 63228 AN XY: 74342

African (AFR) AF: 0.935 AC: 38759 AN: 41466

American (AMR) AF: 0.847 AC: 12934 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2530 AN: 3468

East Asian (EAS) AF: 0.969 AC: 5026 AN: 5188

South Asian (SAS) AF: 0.806 AC: 3882 AN: 4816

European-Finnish (FIN) AF: 0.827 AC: 8751 AN: 10576

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54883 AN: 67978

Other (OTH) AF: 0.810 AC: 1707 AN: 2108

Alfa AF: 0.835 Hom.: 20655

Bravo AF: 0.855

Asia WGS AF: 0.897 AC: 3120 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	4.6
DANN	Benign	0.61
PhyloP100		-0.089
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: rs4902587; hg19: chr14-68905688;