14-68346398-T-C

Variant names:

• chr14-68346398-T-C
• rs1570106
• NM_133510.4:c.853+54418T>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.853+54418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,238 control chromosomes in the GnomAD database, including 54,260 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 0.84 (54260 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 31 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.853+54418T>C		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.853+54418T>C		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.853+54418T>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.853+54418T>C		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.853+54418T>C		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.853+54418T>C		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128021 AN: 152120 Hom.: 54193 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.842 AC: 128147 AN: 152238 Hom.: 54260 Cov.: 32 AF XY: 0.840 AC XY: 62545 AN XY: 74418

African (AFR) AF: 0.913 AC: 37917 AN: 41542

American (AMR) AF: 0.842 AC: 12873 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2480 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5141 AN: 5188

South Asian (SAS) AF: 0.845 AC: 4077 AN: 4826

European-Finnish (FIN) AF: 0.780 AC: 8256 AN: 10584

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54762 AN: 68014

Other (OTH) AF: 0.808 AC: 1707 AN: 2112

Alfa AF: 0.823 Hom.: 73265

Bravo AF: 0.848

Asia WGS AF: 0.894 AC: 3111 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	7.2
DANN	Benign	0.43
PhyloP100		-0.064
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: rs1570106; hg19: chr14-68813115;