chr14-68232877-C-T

Position:

• chr14-68232877-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_133510.4(RAD51B):​c.757-59007C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,234 control chromosomes in the GnomAD database, including 1,337 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 (1337 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.757-59007C>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-59007C>T		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19263 AN: 152116 Hom.: 1335 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.127 AC: 19275 AN: 152234 Hom.: 1337 Cov.: 32 AF XY: 0.127 AC XY: 9432 AN XY: 74414

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.150

Alfa AF: 0.154 Hom.: 2255

Bravo AF: 0.128

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1314913; hg19: chr14-68699594;