14-68573361-T-C

Variant names:

• chr14-68573361-T-C
• rs10130694
• ENST00000487861.5:c.1037-37645T>C

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-37645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,938 control chromosomes in the GnomAD database, including 33,650 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 0.66 (33650 hom., cov: 31)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487861.5. 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
	RAD51B	NM_001321821.2		c.1037-37645T>C		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.1037-21124T>C		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-29302T>C		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.1037-37645T>C		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1037-21124T>C		intron	N/A	ENSP00000419471.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-77420T>C		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 99974 AN: 151820 Hom.: 33631 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.658 AC: 100034 AN: 151938 Hom.: 33650 Cov.: 31 AF XY: 0.658 AC XY: 48864 AN XY: 74280

African (AFR) AF: 0.567 AC: 23486 AN: 41408

American (AMR) AF: 0.660 AC: 10076 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2379 AN: 3464

East Asian (EAS) AF: 0.278 AC: 1434 AN: 5150

South Asian (SAS) AF: 0.726 AC: 3497 AN: 4816

European-Finnish (FIN) AF: 0.680 AC: 7177 AN: 10558

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.730 AC: 49613 AN: 67964

Other (OTH) AF: 0.666 AC: 1404 AN: 2108

Alfa AF: 0.694 Hom.: 23831

Bravo AF: 0.644

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.38
DANN	Benign	0.43
PhyloP100		-1.9
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: rs10130694; hg19: chr14-69040078;