rs12893578

Positions:

• chr14-68637955-A-G
• chr14-68637955-A-T

Variant summary

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

The ENST00000488612.5(RAD51B):​c.1037-12826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,170 control chromosomes in the GnomAD database, including 13,180 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 0.40 (13180 hom., cov: 33)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56

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]

LOC124903333 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903333	XR_007064220.1	n.422T>C		non_coding_transcript_exon_variant	4/4
RAD51B	NM_001321818.2	c.1037-44982A>G		intron_variant			NP_001308747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.1037-12826A>G		intron_variant		1		ENSP00000420061
RAD51B	ENST00000478014.5	n.384-44982A>G		intron_variant, non_coding_transcript_variant		3
RAD51B	ENST00000553595.5	n.614-44982A>G		intron_variant, non_coding_transcript_variant		3
RAD51B	ENST00000554244.5	n.488-44982A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61191 AN: 152052 Hom.: 13183 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.402 AC: 61209 AN: 152170 Hom.: 13180 Cov.: 33 AF XY: 0.410 AC XY: 30492 AN XY: 74384

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.419

Alfa AF: 0.411 Hom.: 9216

Bravo AF: 0.404

Asia WGS AF: 0.597 AC: 2072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12893578; hg19: chr14-69104672;