chr14-68310488-T-G

Variant names:

• chr14-68310488-T-G
• rs7148412
• NM_133510.4:c.853+18508T>G

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+18508T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,056 control chromosomes in the GnomAD database, including 35,431 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 0.68 (35431 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 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+18508T>G		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.853+18508T>G		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.853+18508T>G		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+18508T>G		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.853+18508T>G		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.853+18508T>G		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103361 AN: 151938 Hom.: 35408 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.680 AC: 103427 AN: 152056 Hom.: 35431 Cov.: 32 AF XY: 0.678 AC XY: 50380 AN XY: 74322

African (AFR) AF: 0.612 AC: 25350 AN: 41452

American (AMR) AF: 0.694 AC: 10590 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2853 AN: 5178

South Asian (SAS) AF: 0.694 AC: 3341 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7318 AN: 10564

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.729 AC: 49570 AN: 67994

Other (OTH) AF: 0.654 AC: 1379 AN: 2110

Alfa AF: 0.640 Hom.: 2479

Bravo AF: 0.672

Asia WGS AF: 0.615 AC: 2142 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	2.6
DANN	Benign	0.74
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7148412; hg19: chr14-68777205;