Variant 11-34656955-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012153.6(EHF):c.592C>A(p.His198Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

EHF
NM_012153.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13782826).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHF	NM_012153.6 linkuse as main transcript	c.592C>A	p.His198Asn	missense_variant	7/9	ENST00000257831.8	NP_036285.2	Q9NZC4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHF	ENST00000257831.8 linkuse as main transcript	c.592C>A	p.His198Asn	missense_variant	7/9	1	NM_012153.6	ENSP00000257831.3		Q9NZC4-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250632

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461334

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.658C>A (p.H220N) alteration is located in exon 7 (coding exon 7) of the EHF gene. This alteration results from a C to A substitution at nucleotide position 658, causing the histidine (H) at amino acid position 220 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0081

T;.;T;T;.

Eigen

Benign

-0.072

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

.;T;.;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.060

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.099

T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.049

B;B;B;B;.

Vest4

0.38

MutPred

0.39

Loss of ubiquitination at K200 (P = 0.1016);.;Loss of ubiquitination at K200 (P = 0.1016);Loss of ubiquitination at K200 (P = 0.1016);.;

MVP

0.39

MPC

0.53

ClinPred

0.14

GERP RS

5.7

Varity_R

0.13

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over