rs17105852

Positions:

• chr14-68563935-C-A
• chr14-68563935-C-T

Variant summary

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

The NM_001321821.2(RAD51B):​c.1037-47071C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 982,132 control chromosomes in the GnomAD database, including 648 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 0.044 (180 hom., cov: 33)
  • Exomes 𝑓: 0.032 (468 hom.)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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]

LOC124903335 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-47071C>A		intron_variant			NP_001308750.1
RAD51B	NM_133509.5	c.1037-30550C>A		intron_variant			NP_598193.2
RAD51B	NM_001321809.2	c.1037-38728C>A		intron_variant			NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-47071C>A		intron_variant		1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-30550C>A		intron_variant		1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-86846C>A		intron_variant		1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6667 AN: 152210 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0317 AC: 26314 AN: 829804 Hom.: 468 Cov.: 28 AF XY: 0.0317 AC XY: 12169 AN XY: 383322

Gnomad4 AFR exome AF: 0.0669

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0559

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0250

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0438 AC: 6677 AN: 152328 Hom.: 180 Cov.: 33 AF XY: 0.0431 AC XY: 3213 AN XY: 74486

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.0362

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0185 Hom.: 7

Bravo AF: 0.0455

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17105852; hg19: chr14-69030652;