rs1290999

Positions:

• chr14-68579159-A-G
• chr14-68579159-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487861.5(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 ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_001321809.2	c.1037-23504A>G		intron_variant
RAD51B	NM_001321810.2	c.1037-23504A>G		intron_variant
RAD51B	NM_001321815.1	c.923-31999A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000487270.5	c.1037-15326A>G		intron_variant		1
RAD51B	ENST00000487861.5	c.1037-31847A>G		intron_variant		1
RAD51B	ENST00000488612.5	c.1037-71622A>G		intron_variant		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

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.766

Alfa AF: 0.780 Hom.: 51435

Bravo AF: 0.775

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1290999; hg19: chr14-69045876;