Variant rs397792796 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_024757.5(EHMT1):c.3541-11_3541-10dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,306 control chromosomes in the GnomAD database, including 18,014 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4782 hom., cov: 30)

Exomes 𝑓: 0.11 ( 13232 hom. )

Consequence

EHMT1
NM_024757.5 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.314

Variant links:

Genes affected

EHMT1 (HGNC:24650): (euchromatic histone lysine methyltransferase 1) The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

EHMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-137834335-T-TTC is Benign according to our data. Variant chr9-137834335-T-TTC is described in ClinVar as [Benign]. Clinvar id is 96157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT1	NM_024757.5 linkuse as main transcript	c.3541-11_3541-10dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000460843.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000460843.6 linkuse as main transcript	c.3541-11_3541-10dup		splice_polypyrimidine_tract_variant, intron_variant		5	NM_024757.5		Q9H9B1-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30918

AN:

152088

Hom.:

4752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.0848

Gnomad EAS

AF:

0.0117

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.147

AC:

36202

AN:

246224

Hom.:

4566

AF XY:

0.132

AC XY:

17715

AN XY:

134032

show subpopulations

Gnomad AFR exome

AF:

0.436

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.0982

Gnomad FIN exome

AF:

0.0619

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.115

AC:

167532

AN:

1460102

Hom.:

13232

Cov.:

AF XY:

0.112

AC XY:

81495

AN XY:

726456

show subpopulations

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.0836

Gnomad4 EAS exome

AF:

0.00917

Gnomad4 SAS exome

AF:

0.0978

Gnomad4 FIN exome

AF:

0.0663

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.204

AC:

31012

AN:

152204

Hom.:

4782

Cov.:

AF XY:

0.199

AC XY:

14808

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.0848

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0644

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.149

Hom.:

434

Asia WGS

AF:

0.0920

AC:

318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 25, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Kleefstra syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 17, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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