chr14-68495787-T-G

Variant names:

• chr14-68495787-T-G
• rs3784131
• ENST00000487861.5:c.1036+27537T>G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1036+27537T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,102 control chromosomes in the GnomAD database, including 1,740 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 0.13 (1740 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1036+27537T>G		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1036+27537T>G		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321812.1	c.1036+27537T>G		intron_variant	Intron 9 of 9		NP_001308741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+27537T>G		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+27537T>G		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+27537T>G		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19819 AN: 151984 Hom.: 1740 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.130 AC: 19833 AN: 152102 Hom.: 1740 Cov.: 32 AF XY: 0.134 AC XY: 9971 AN XY: 74350

African (AFR) AF: 0.0675 AC: 2801 AN: 41526

American (AMR) AF: 0.155 AC: 2366 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3462

East Asian (EAS) AF: 0.516 AC: 2660 AN: 5152

South Asian (SAS) AF: 0.148 AC: 711 AN: 4808

European-Finnish (FIN) AF: 0.170 AC: 1792 AN: 10568

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8631 AN: 67986

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.130 Hom.: 1265

Bravo AF: 0.130

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		0.36
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: rs3784131; hg19: chr14-68962504;