14-67823747-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133510.4(RAD51B):c.84+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 729,970 control chromosomes in the GnomAD database, including 39,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8338 hom., cov: 32)
  • Exomes 𝑓: 0.32 (31033 hom.)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.907

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 14-67823747-G-A is Benign according to our data. Variant chr14-67823747-G-A is described in ClinVar as [Benign]. Clinvar id is 1271766.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
RAD51B	NM_133510.4	c.84+120G>A		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.84+120G>A		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49216 AN: 151930 Hom.: 8317 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: 0.0750

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.317 AC: 183403 AN: 577922 Hom.: 31033 AF XY: 0.315 AC XY: 94250 AN XY: 299270

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.0868

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.324 AC: 49270 AN: 152048 Hom.: 8338 Cov.: 32 AF XY: 0.316 AC XY: 23494 AN XY: 74324

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.326

Alfa AF: 0.335 Hom.: 1052

Bravo AF: 0.323

Asia WGS AF: 0.179 AC: 622 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	14
Dann	Benign	0.79

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: rs28623567; hg19: chr14-68290464;