14-68494848-T-C

Variant names:

• chr14-68494848-T-C
• rs2331706
• ENST00000487861.5:c.1036+26598T>C

Variant summary

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

The NM_001321821.2(RAD51B):​c.1036+26598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,568 control chromosomes in the GnomAD database, including 34,322 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 0.66 (34322 hom., cov: 28)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321821.2. 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_001321821.2		c.1036+26598T>C		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.1036+26598T>C		intron	N/A	NP_598193.2
	RAD51B	NM_001321812.1		c.1036+26598T>C		intron	N/A	NP_001308741.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1036+26598T>C		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.1036+26598T>C		intron	N/A	ENSP00000419471.1	O15315-3
	RAD51B	ENST00000488612.5	TSL:1	c.1036+26598T>C		intron	N/A	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100114 AN: 151450 Hom.: 34274 Cov.: 28

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.661 AC: 100214 AN: 151568 Hom.: 34322 Cov.: 28 AF XY: 0.656 AC XY: 48581 AN XY: 74008

African (AFR) AF: 0.851 AC: 35145 AN: 41316

American (AMR) AF: 0.539 AC: 8205 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2060 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3066 AN: 5100

South Asian (SAS) AF: 0.429 AC: 2056 AN: 4792

European-Finnish (FIN) AF: 0.629 AC: 6572 AN: 10442

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40915 AN: 67916

Other (OTH) AF: 0.655 AC: 1377 AN: 2102

Alfa AF: 0.610 Hom.: 44902

Bravo AF: 0.668

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2331706; hg19: chr14-68961565;