rs4876902

chr9-137816151-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024757.5(EHMT1):c.3374+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,231,248 control chromosomes in the GnomAD database, including 33,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3775 hom., cov: 33)
  • Exomes 𝑓: 0.23 (29509 hom.)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.16

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-137816151-C-T is Benign according to our data. Variant chr9-137816151-C-T is described in ClinVar as [Benign]. Clinvar id is 1255100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT1	NM_024757.5	c.3374+89C>T		intron_variant		ENST00000460843.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000460843.6	c.3374+89C>T		intron_variant		5	NM_024757.5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31554 AN: 152094 Hom.: 3771 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.225 AC: 242974 AN: 1079036 Hom.: 29509 Cov.: 14 AF XY: 0.228 AC XY: 124656 AN XY: 545994

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.0945

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.207 AC: 31576 AN: 152212 Hom.: 3775 Cov.: 33 AF XY: 0.211 AC XY: 15723 AN XY: 74434

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.215

Alfa AF: 0.232 Hom.: 2519

Bravo AF: 0.212

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.36
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs4876902; hg19: chr9-140710603; COSMIC: COSV71777913; COSMIC: COSV71777913;