Genetic Variant NM_024757.5:c.-5G>A (chr9-137619024-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024757.5(EHMT1):c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 972,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

EHMT1
NM_024757.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.82

Publications

0 publications found

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:

ENSG00000283411 (HGNC:):

ENSG00000283411 links:

ARRDC1-AS1 (HGNC:23395): (ARRDC1 antisense RNA 1) This transcribed locus is thought to be non-coding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ARRDC1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024757.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EHMT1	NM_024757.5	MANE Select	c.-5G>A	5_prime_UTR	Exon 1 of 27	NP_079033.4
EHMT1	NM_001354263.2		c.-5G>A	5_prime_UTR	Exon 1 of 27	NP_001341192.1
EHMT1	NM_001354259.2		c.-34G>A	5_prime_UTR	Exon 1 of 16	NP_001341188.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EHMT1	ENST00000460843.6	TSL:5 MANE Select	c.-5G>A	5_prime_UTR	Exon 1 of 27	ENSP00000417980.1	Q9H9B1-1
EHMT1	ENST00000462484.5	TSL:1	c.-5G>A	5_prime_UTR	Exon 1 of 16	ENSP00000417328.1	Q9H9B1-4
EHMT1	ENST00000896765.1		c.-5G>A	5_prime_UTR	Exon 1 of 28	ENSP00000566824.1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000968

AC:

AN:

826046

Hom.:

Cov.:

AF XY:

0.00000262

AC XY:

AN XY:

382062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15610

American (AMR)

AF:

0.00

AC:

AN:

1102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5184

East Asian (EAS)

AF:

0.00

AC:

AN:

3692

South Asian (SAS)

AF:

0.000117

AC:

AN:

17060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.00000663

AC:

AN:

754044

Other (OTH)

AF:

0.0000369

AC:

AN:

27100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000136

AC:

AN:

146526

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40944

American (AMR)

AF:

0.00

AC:

AN:

14770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.000393

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65858

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.8

PromoterAI

0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over