rs10483821

Variant names:

• chr14-68727890-C-G
• rs10483821
• ENST00000488612.5:c.*12-1918C>G

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*12-1918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,182 control chromosomes in the GnomAD database, including 1,891 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 0.15 (1891 hom., cov: 32)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 5 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

LOC105370547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488612.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.*12-1918C>G		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22947 AN: 152064 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0724

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.151 AC: 22952 AN: 152182 Hom.: 1891 Cov.: 32 AF XY: 0.156 AC XY: 11577 AN XY: 74398

African (AFR) AF: 0.162 AC: 6746 AN: 41528

American (AMR) AF: 0.0861 AC: 1316 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 251 AN: 3468

East Asian (EAS) AF: 0.183 AC: 948 AN: 5176

South Asian (SAS) AF: 0.143 AC: 690 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2986 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9678 AN: 68008

Other (OTH) AF: 0.122 AC: 258 AN: 2114

Alfa AF: 0.148 Hom.: 206

Bravo AF: 0.134

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.40
PhyloP100		-0.48
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: rs10483821; hg19: chr14-69194607;