Menu
GeneBe

12-121440835-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_032590.5(KDM2B):c.3591G>A(p.Pro1197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,612,008 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

KDM2B
NM_032590.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-121440835-C-T is Benign according to our data. Variant chr12-121440835-C-T is described in ClinVar as [Benign]. Clinvar id is 3034878.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.02 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 308 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KDM2BNM_032590.5 linkuse as main transcriptc.3591G>A p.Pro1197= synonymous_variant 21/23 ENST00000377071.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KDM2BENST00000377071.9 linkuse as main transcriptc.3591G>A p.Pro1197= synonymous_variant 21/231 NM_032590.5 P1Q8NHM5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00202
AC:
308
AN:
152160
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00702
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000547
AC:
135
AN:
246822
Hom.:
0
AF XY:
0.000396
AC XY:
53
AN XY:
133970
show subpopulations
Gnomad AFR exome
AF:
0.00757
Gnomad AMR exome
AF:
0.000349
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.000176
AC:
257
AN:
1459730
Hom.:
2
Cov.:
29
AF XY:
0.000149
AC XY:
108
AN XY:
726102
show subpopulations
Gnomad4 AFR exome
AF:
0.00637
Gnomad4 AMR exome
AF:
0.000381
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00202
AC:
308
AN:
152278
Hom.:
3
Cov.:
32
AF XY:
0.00187
AC XY:
139
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00700
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000942
Hom.:
0
Bravo
AF:
0.00228

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

KDM2B-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 09, 2019This 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
-0.61
Cadd
Benign
2.6
Dann
Benign
0.59

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.

Other links and lift over

dbSNP: rs141490235; hg19: chr12-121878638; COSMIC: COSV100997632; COSMIC: COSV100997632; API