rs8022206

Positions:

• chr14-68054189-G-A

Variant summary

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

The NM_133510.4(RAD51B):​c.756+166985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,066 control chromosomes in the GnomAD database, including 2,473 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 0.17 (2473 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.756+166985G>A		intron_variant		ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.756+166985G>A		intron_variant		1	NM_133510.4	ENSP00000418859	P4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26356 AN: 151948 Hom.: 2459 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.174 AC: 26408 AN: 152066 Hom.: 2473 Cov.: 32 AF XY: 0.172 AC XY: 12753 AN XY: 74314

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.206

Alfa AF: 0.180 Hom.: 2598

Bravo AF: 0.180

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs8022206; hg19: chr14-68520906;