Variant 11-95025682-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001161630.1(KDM4E):c.125A>G(p.Gln42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,548,226 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.012 ( 50 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 30 hom. )

Consequence

KDM4E
NM_001161630.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

KDM4E (HGNC:37098): (lysine demethylase 4E) The protein encoded by this intronless gene is a member of a large family of histone lysine demethylases, which use oxygen and 2-oxoglutarate to demethylate di- and trimethylated lys9 of histone H3. Derepression of genes by demethylases is sometimes involved in viral infection or carcinogenesis, so inhibitors of these enzymes are desired. [provided by RefSeq, Dec 2016]

KDM4E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020182133).

BP6

Variant 11-95025682-A-G is Benign according to our data. Variant chr11-95025682-A-G is described in ClinVar as [Benign]. Clinvar id is 781030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1741/151246) while in subpopulation AFR AF= 0.0386 (1594/41250). AF 95% confidence interval is 0.0371. There are 50 homozygotes in gnomad4. There are 851 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4E	NM_001161630.1 linkuse as main transcript	c.125A>G	p.Gln42Arg	missense_variant	1/1	ENST00000450979.2	NP_001155102.1	B2RXH2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4E	ENST00000450979.2 linkuse as main transcript	c.125A>G	p.Gln42Arg	missense_variant	1/1	6	NM_001161630.1	ENSP00000397239.2		B2RXH2

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1741

AN:

151128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00495

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000422

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000649

Gnomad OTH

AF:

0.00625

GnomAD3 exomes

AF:

0.00325

AC:

543

AN:

167088

Hom.:

AF XY:

0.00275

AC XY:

246

AN XY:

89512

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.00360

Gnomad ASJ exome

AF:

0.00280

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00151

AC:

2108

AN:

1396980

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

956

AN XY:

690848

show subpopulations

Gnomad4 AFR exome

AF:

0.0363

Gnomad4 AMR exome

AF:

0.00410

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.0000542

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0115

AC:

1741

AN:

151246

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

851

AN XY:

73898

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.00494

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000423

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000649

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.00113

Hom.:

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0412

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.00319

AC:

377

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0080

DANN

Benign

0.097

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.7

PrimateAI

Benign

0.38

PROVEAN

Benign

3.0

REVEL

Benign

0.041

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.052

MVP

0.043

MPC

0.38

ClinPred

0.0051

GERP RS

0.20

Varity_R

0.083

gMVP

0.087

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