chr14-68352517-T-C

Variant names:

• chr14-68352517-T-C
• rs4902571
• NM_133510.4:c.854-58907T>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.854-58907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,322 control chromosomes in the GnomAD database, including 57,167 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 0.86 (57167 hom., cov: 33)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.854-58907T>C		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.854-58907T>C		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.854-58907T>C		intron	N/A	NP_598193.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.854-58907T>C		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.854-58907T>C		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.854-58907T>C		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131466 AN: 152204 Hom.: 57098 Cov.: 33

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.864 AC: 131596 AN: 152322 Hom.: 57167 Cov.: 33 AF XY: 0.863 AC XY: 64319 AN XY: 74488

African (AFR) AF: 0.953 AC: 39611 AN: 41582

American (AMR) AF: 0.860 AC: 13163 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2626 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5155 AN: 5188

South Asian (SAS) AF: 0.806 AC: 3894 AN: 4832

European-Finnish (FIN) AF: 0.843 AC: 8940 AN: 10610

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55533 AN: 68014

Other (OTH) AF: 0.825 AC: 1743 AN: 2114

Alfa AF: 0.824 Hom.: 88152

Bravo AF: 0.869

Asia WGS AF: 0.903 AC: 3142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.74
PhyloP100		-0.51
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: rs4902571; hg19: chr14-68819234;