12-121500382-C-G

Position:

• chr12-121500382-C-G

Variant summary

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

The NM_032590.5(KDM2B):​c.1648-5717G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,192 control chromosomes in the GnomAD database, including 8,595 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 0.30 (8595 hom., cov: 32)
• Consequence: KDM2B NM_032590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

Genes affected

KDM2B (HGNC:13610): (lysine demethylase 2B) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM2B	NM_032590.5	c.1648-5717G>C		intron_variant		ENST00000377071.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM2B	ENST00000377071.9	c.1648-5717G>C		intron_variant		1	NM_032590.5	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46009 AN: 152074 Hom.: 8588 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.302 AC: 46016 AN: 152192 Hom.: 8595 Cov.: 32 AF XY: 0.301 AC XY: 22407 AN XY: 74394

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.359

Alfa AF: 0.339 Hom.: 1223

Bravo AF: 0.303

Asia WGS AF: 0.283 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.70

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: rs10849893; hg19: chr12-121938185;