14-68579159-A-G

Variant names:

• chr14-68579159-A-G
• rs1290999
• ENST00000487861.5:c.1037-31847A>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.1037-31847A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,072 control chromosomes in the GnomAD database, including 46,950 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 0.78 (46950 hom., cov: 31)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_001321821.2		c.1037-31847A>G		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.1037-15326A>G		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-23504A>G		intron	N/A	NP_001308738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-31847A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1037-15326A>G		intron	N/A	ENSP00000419471.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-71622A>G		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118497 AN: 151954 Hom.: 46900 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.780 AC: 118593 AN: 152072 Hom.: 46950 Cov.: 31 AF XY: 0.775 AC XY: 57598 AN XY: 74318

African (AFR) AF: 0.842 AC: 34948 AN: 41490

American (AMR) AF: 0.732 AC: 11181 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1582 AN: 5160

South Asian (SAS) AF: 0.757 AC: 3654 AN: 4824

European-Finnish (FIN) AF: 0.726 AC: 7668 AN: 10566

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.799 AC: 54320 AN: 67972

Other (OTH) AF: 0.766 AC: 1613 AN: 2106

Alfa AF: 0.782 Hom.: 63175

Bravo AF: 0.775

Asia WGS AF: 0.560 AC: 1947 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	1.0
DANN	Benign	0.76
PhyloP100		-0.32
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: rs1290999; hg19: chr14-69045876;