NM_012153.6:c.578C>G

Variant names:

• chr11-34656941-C-G
• rs1257901011
• NM_012153.6:c.578C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012153.6(EHF):​c.578C>G​(p.Pro193Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,392 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P193H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EHF NM_012153.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

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]

ENSG00000309708 (HGNC:):

ACMG classification

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=0.0666464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHF	NM_012153.6	c.578C>G	p.Pro193Arg	missense_variant	Exon 7 of 9	ENST00000257831.8	NP_036285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHF	ENST00000257831.8	c.578C>G	p.Pro193Arg	missense_variant	Exon 7 of 9	1	NM_012153.6	ENSP00000257831.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461392 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111778

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.65
DEOGEN2	Benign	0.0055	T;.;T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	.;T;.;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N;N;.
PhyloP100		3.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.9	N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.41	T;T;T;T;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.026	B;B;B;B;.
Vest4		0.24
MutPred		0.28		Gain of MoRF binding (P = 0.0158);.;Gain of MoRF binding (P = 0.0158);Gain of MoRF binding (P = 0.0158);.;
MVP		0.23
MPC		0.43
ClinPred		0.14	T
GERP RS		4.6
Varity_R		0.063
gMVP		0.23
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1257901011; hg19: chr11-34678488;