Variant 11-34656941-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012153.6(EHF):c.578C>A(p.Pro193His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

EHF
NM_012153.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05377665).

BP6

Variant 11-34656941-C-A is Benign according to our data. Variant chr11-34656941-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2340133.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHF	NM_012153.6 linkuse as main transcript	c.578C>A	p.Pro193His	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.578C>A	p.Pro193His	missense_variant	7/9	1	NM_012153.6	ENSP00000257831.3		Q9NZC4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726986

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0056

T;.;T;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.60

.;T;.;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.054

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

N;.;N;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

N;N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.37

T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.21

MutPred

0.22

Loss of catalytic residue at P193 (P = 0.0199);.;Loss of catalytic residue at P193 (P = 0.0199);Loss of catalytic residue at P193 (P = 0.0199);.;

MVP

0.13

MPC

0.45

ClinPred

0.24

GERP RS

4.6

Varity_R

0.11

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