chr14-67823709-T-C

Position:

• chr14-67823709-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133510.4(RAD51B):​c.84+82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,017,120 control chromosomes in the GnomAD database, including 56,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8326 hom., cov: 32)
  • Exomes 𝑓: 0.32 (48406 hom.)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.204

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-67823709-T-C is Benign according to our data. Variant chr14-67823709-T-C is described in ClinVar as [Benign]. Clinvar id is 1270487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.84+82T>C		intron_variant		ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.84+82T>C		intron_variant		1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49189 AN: 151970 Hom.: 8305 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.0744

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.324 AC: 280573 AN: 865032 Hom.: 48406 AF XY: 0.322 AC XY: 142810 AN XY: 443314

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.0850

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.324 AC: 49243 AN: 152088 Hom.: 8326 Cov.: 32 AF XY: 0.316 AC XY: 23474 AN XY: 74346

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.0747

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.326

Alfa AF: 0.335 Hom.: 1056

Bravo AF: 0.323

Asia WGS AF: 0.179 AC: 622 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.53

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: rs28604984; hg19: chr14-68290426;