rs4634736

chr9-137707193-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024757.5(EHMT1):c.22-3774G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,256 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (836 hom., cov: 33)
• Consequence: EHMT1 NM_024757.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHMT1	NM_024757.5	c.22-3774G>A		intron_variant		ENST00000460843.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHMT1	ENST00000460843.6	c.22-3774G>A		intron_variant		5	NM_024757.5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15313 AN: 152138 Hom.: 837 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15320 AN: 152256 Hom.: 836 Cov.: 33 AF XY: 0.0977 AC XY: 7273 AN XY: 74444

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0995 Hom.: 805

Bravo AF: 0.104

Asia WGS AF: 0.0400 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.5
Dann	Benign	0.53

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: rs4634736; hg19: chr9-140601645;