chr14-68440049-C-T

Position:

• chr14-68440049-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):​c.958-28123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,258 control chromosomes in the GnomAD database, including 55,397 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 0.85 (55397 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.958-28123C>T		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.958-28123C>T		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129416 AN: 152140 Hom.: 55329 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.851 AC: 129546 AN: 152258 Hom.: 55397 Cov.: 32 AF XY: 0.850 AC XY: 63307 AN XY: 74438

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.810

Alfa AF: 0.850 Hom.: 10269

Bravo AF: 0.855

Asia WGS AF: 0.897 AC: 3120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.1
DANN	Benign	0.73

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: rs2331703; hg19: chr14-68906766;