Variant chr12-121440856-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_032590.5(KDM2B):c.3570G>A(p.Gln1190Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,502 control chromosomes in the GnomAD database, including 122,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9683 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112916 hom. )

Consequence

KDM2B
NM_032590.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.30

Variant links:

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]

KDM2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 12-121440856-C-T is Benign according to our data. Variant chr12-121440856-C-T is described in ClinVar as [Benign]. Clinvar id is 3060938.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM2B	NM_032590.5 link	c.3570G>A	p.Gln1190Gln	synonymous_variant	21/23	ENST00000377071.9	NP_115979.3	Q8NHM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM2B	ENST00000377071.9 link	c.3570G>A	p.Gln1190Gln	synonymous_variant	21/23	1	NM_032590.5	ENSP00000366271.3		Q8NHM5-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52173

AN:

151980

Hom.:

9682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.392

AC:

97424

AN:

248616

Hom.:

20001

AF XY:

0.387

AC XY:

52224

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.449

Gnomad SAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.389

AC:

568348

AN:

1461404

Hom.:

112916

Cov.:

AF XY:

0.386

AC XY:

280924

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.464

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.343

AC:

52200

AN:

152098

Hom.:

9683

Cov.:

AF XY:

0.347

AC XY:

25774

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.386

Gnomad4 EAS

AF:

0.434

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.364

Hom.:

10869

Bravo

AF:

0.329

Asia WGS

AF:

0.372

AC:

1289

AN:

3478

EpiCase

AF:

0.365

EpiControl

AF:

0.362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KDM2B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.8

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over