14-68653768-C-T

Variant names:

• chr14-68653768-C-T
• rs2180611
• ENST00000488612.5:c.*11+2912C>T

Variant summary

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

The NM_001321818.2(RAD51B):​c.1037-29169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,152 control chromosomes in the GnomAD database, including 11,848 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 0.38 (11848 hom., cov: 33)
• Consequence: RAD51B NM_001321818.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 6 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

RAD51B-AS1 (HGNC:58171):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321818.2. 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_001321818.2		c.1037-29169C>T		intron	N/A	NP_001308747.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.*11+2912C>T		intron	N/A	ENSP00000420061.1	O15315-4
	RAD51B	ENST00000478014.5	TSL:3	n.384-29169C>T		intron	N/A
	RAD51B	ENST00000553595.5	TSL:3	n.614-29169C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57900 AN: 152034 Hom.: 11844 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.381 AC: 57916 AN: 152152 Hom.: 11848 Cov.: 33 AF XY: 0.389 AC XY: 28941 AN XY: 74400

African (AFR) AF: 0.294 AC: 12217 AN: 41506

American (AMR) AF: 0.460 AC: 7024 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3979 AN: 5186

South Asian (SAS) AF: 0.559 AC: 2695 AN: 4820

European-Finnish (FIN) AF: 0.389 AC: 4124 AN: 10588

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24607 AN: 67980

Other (OTH) AF: 0.400 AC: 847 AN: 2116

Alfa AF: 0.377 Hom.: 44911

Bravo AF: 0.382

Asia WGS AF: 0.609 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-0.46
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: rs2180611; hg19: chr14-69120485;