Genetic Variant EHF:p.Asp145Glu (chr11-34651570-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012153.6(EHF):c.435C>G(p.Asp145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. D145D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EHF
NM_012153.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.642

Publications

0 publications found

Variant links:

Genes affected

EHF (HGNC:3246): (ETS homologous factor) This gene encodes a protein that belongs to an ETS transcription factor subfamily characterized by epithelial-specific expression (ESEs). The encoded protein acts as a transcriptional repressor and may be involved in epithelial differentiation and carcinogenesis. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

EHF links:

ENSG00000309708 (HGNC:):

ENSG00000309708 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038152963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012153.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHF	NM_012153.6	MANE Select	c.435C>G	p.Asp145Glu	missense	Exon 5 of 9	NP_036285.2
EHF	NM_001206616.2		c.501C>G	p.Asp167Glu	missense	Exon 5 of 9	NP_001193545.1	Q9NZC4-3
EHF	NM_001378052.1		c.501C>G	p.Asp167Glu	missense	Exon 5 of 9	NP_001364981.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHF	ENST00000257831.8	TSL:1 MANE Select	c.435C>G	p.Asp145Glu	missense	Exon 5 of 9	ENSP00000257831.3	Q9NZC4-1
EHF	ENST00000531794.5	TSL:1	c.501C>G	p.Asp167Glu	missense	Exon 5 of 9	ENSP00000435835.1	Q9NZC4-3
EHF	ENST00000530286.5	TSL:1	c.435C>G	p.Asp145Glu	missense	Exon 5 of 9	ENSP00000433508.1	Q9NZC4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251270

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111836

Other (OTH)

AF:

0.00

AC:

AN:

60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.67

M_CAP

Benign

0.0066

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.26

PhyloP100

0.64

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.73

REVEL

Benign

0.062

Sift

Benign

0.62

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.23

MutPred

0.32

Gain of methylation at K144 (P = 0.1208)

MVP

0.33

MPC

0.36

ClinPred

0.027

GERP RS

1.3

Varity_R

0.041

gMVP

0.089

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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