Variant 6-18161343-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001364614.2(KDM1B):c.104C>T(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,848 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 19 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 22 hom. )

Consequence

KDM1B
NM_001364614.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

KDM1B (HGNC:21577): (lysine demethylase 1B) Flavin-dependent histone demethylases, such as KDM1B, regulate histone lysine methylation, an epigenetic mark that regulates gene expression and chromatin function (Karytinos et al., 2009 [PubMed 19407342]).[supplied by OMIM, Oct 2009]

KDM1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032545626).

BP6

Variant 6-18161343-C-T is Benign according to our data. Variant chr6-18161343-C-T is described in ClinVar as [Benign]. Clinvar id is 784064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.009 (1370/152150) while in subpopulation AFR AF= 0.0308 (1276/41488). AF 95% confidence interval is 0.0294. There are 19 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM1B	NM_001364614.2 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/22	ENST00000650836.2	NP_001351543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDM1B	ENST00000650836.2 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/22		NM_001364614.2	ENSP00000499208.1	Q8NB78-1
KDM1B	ENST00000546309.6 linkuse as main transcript	c.-19+5930C>T		intron_variant		1		ENSP00000442670.1	Q08EI0
KDM1B	ENST00000449850.2 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/22	5		ENSP00000405669.2	H0Y6H0
KDM1B	ENST00000297792.9 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/18	2		ENSP00000297792.5	Q8NB78-2

Frequencies

GnomAD3 genomes

AF:

0.00898

AC:

1366

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00247

AC:

620

AN:

251400

Hom.:

AF XY:

0.00177

AC XY:

241

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00123

AC:

1791

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

811

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000308

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00900

AC:

1370

AN:

152150

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

642

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.0104

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0277

AC:

122

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00306

AC:

371

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.41

.;N

REVEL

Benign

0.074

Sift

Uncertain

0.023

.;D

Sift4G

Uncertain

0.044

.;D

Vest4

0.071

MVP

0.043

MPC

0.70

ClinPred

0.015

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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