ENST00000462942.3:n.2398-6851T>C

Variant names:

• chr9-137839709-T-C
• rs4526432
• ENST00000462942.3:n.2398-6851T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462942.3(EHMT1):​n.2398-6851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,014 control chromosomes in the GnomAD database, including 19,881 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 0.50 (19881 hom., cov: 32)
• Consequence: EHMT1 ENST00000462942.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Kleefstra syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Kleefstra syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000462942.3	n.2398-6851T>C		intron_variant	Intron 20 of 21	2		ENSP00000436107.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76566 AN: 151898 Hom.: 19852 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.504 AC: 76650 AN: 152014 Hom.: 19881 Cov.: 32 AF XY: 0.508 AC XY: 37734 AN XY: 74312

African (AFR) AF: 0.594 AC: 24617 AN: 41444

American (AMR) AF: 0.385 AC: 5883 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3903 AN: 5164

South Asian (SAS) AF: 0.593 AC: 2848 AN: 4804

European-Finnish (FIN) AF: 0.525 AC: 5542 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 155 AN: 290

European-Non Finnish (NFE) AF: 0.449 AC: 30531 AN: 67982

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.470 Hom.: 68722

Bravo AF: 0.497

Asia WGS AF: 0.691 AC: 2396 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	1.6
DANN	Benign	0.69
PhyloP100		-0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4526432; hg19: chr9-140734161;