14-68210775-G-C

Variant names:

• chr14-68210775-G-C
• rs1298340
• NM_133510.4:c.757-81109G>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.757-81109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,112 control chromosomes in the GnomAD database, including 2,004 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 0.16 (2004 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.757-81109G>C		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.757-81109G>C		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.757-81109G>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.757-81109G>C		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.757-81109G>C		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.757-81109G>C		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23908 AN: 151994 Hom.: 2002 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.157 AC: 23926 AN: 152112 Hom.: 2004 Cov.: 32 AF XY: 0.156 AC XY: 11586 AN XY: 74368

African (AFR) AF: 0.182 AC: 7561 AN: 41484

American (AMR) AF: 0.161 AC: 2465 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3468

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5182

South Asian (SAS) AF: 0.164 AC: 791 AN: 4812

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10584

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10162 AN: 67978

Other (OTH) AF: 0.184 AC: 388 AN: 2110

Alfa AF: 0.0542 Hom.: 55

Bravo AF: 0.163

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.11
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: rs1298340; hg19: chr14-68677492;