rs10483813

Variant names:

• chr14-68564567-T-A
• rs10483813
• ENST00000487861.5:c.1037-46439T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68564567-T-A
• chr14-68564567-T-C

Variant summary

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

The NM_001321821.2(RAD51B):​c.1037-46439T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,188 control chromosomes in the GnomAD database, including 2,689 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 (2689 hom., cov: 32)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.63
• Publications: 43 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

LOC124903335 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 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.1037-46439T>A		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.1037-29918T>A		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-38096T>A		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.1037-46439T>A		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.1037-29918T>A		intron	N/A	ENSP00000419471.1	O15315-3
	RAD51B	ENST00000488612.5	TSL:1	c.1037-86214T>A		intron	N/A	ENSP00000420061.1	O15315-4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26096 AN: 152070 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.172 AC: 26122 AN: 152188 Hom.: 2689 Cov.: 32 AF XY: 0.170 AC XY: 12670 AN XY: 74410

African (AFR) AF: 0.0755 AC: 3135 AN: 41546

American (AMR) AF: 0.177 AC: 2702 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3468

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5170

South Asian (SAS) AF: 0.153 AC: 739 AN: 4822

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16306 AN: 67988

Other (OTH) AF: 0.162 AC: 343 AN: 2112

Alfa AF: 0.121 Hom.: 237

Bravo AF: 0.164

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0040
DANN	Benign	0.75
PhyloP100		-4.6
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: rs10483813; hg19: chr14-69031284;