14-68593485-A-G

Variant names:

• chr14-68593485-A-G
• rs4899246
• ENST00000487861.5:c.1037-17521A>G

Variant summary

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

The NM_001321821.2(RAD51B):​c.1037-17521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,140 control chromosomes in the GnomAD database, including 3,192 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 0.20 (3192 hom., cov: 32)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 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.1037-17521A>G		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.1037-1000A>G		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-9178A>G		intron	N/A	NP_001308738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-17521A>G		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.1037-1000A>G		intron	N/A	ENSP00000419471.1	O15315-3
	RAD51B	ENST00000488612.5	TSL:1	c.1037-57296A>G		intron	N/A	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30291 AN: 152022 Hom.: 3191 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.199 AC: 30313 AN: 152140 Hom.: 3192 Cov.: 32 AF XY: 0.197 AC XY: 14651 AN XY: 74370

African (AFR) AF: 0.179 AC: 7411 AN: 41500

American (AMR) AF: 0.184 AC: 2814 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3468

East Asian (EAS) AF: 0.0930 AC: 481 AN: 5174

South Asian (SAS) AF: 0.105 AC: 506 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2099 AN: 10572

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15581 AN: 67982

Other (OTH) AF: 0.188 AC: 397 AN: 2114

Alfa AF: 0.212 Hom.: 1950

Bravo AF: 0.198

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.44
PhyloP100		-1.3
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: rs4899246; hg19: chr14-69060202;