chr14-68508657-C-T

Variant names:

• chr14-68508657-C-T
• rs2842346
• ENST00000487861.5:c.1036+40407C>T

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1036+40407C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,088 control chromosomes in the GnomAD database, including 2,907 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 (2907 hom., cov: 31)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 11 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1036+40407C>T		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1036+40407C>T		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321812.1	c.1037-31543C>T		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+40407C>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+40407C>T		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+40407C>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26316 AN: 151970 Hom.: 2907 Cov.: 31

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.173 AC: 26305 AN: 152088 Hom.: 2907 Cov.: 31 AF XY: 0.173 AC XY: 12856 AN XY: 74352

African (AFR) AF: 0.0459 AC: 1904 AN: 41524

American (AMR) AF: 0.178 AC: 2721 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3470

East Asian (EAS) AF: 0.101 AC: 523 AN: 5170

South Asian (SAS) AF: 0.107 AC: 517 AN: 4824

European-Finnish (FIN) AF: 0.285 AC: 3015 AN: 10562

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16307 AN: 67938

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.216 Hom.: 8261

Bravo AF: 0.158

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.23
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: rs2842346; hg19: chr14-68975374;