11-34646624-C-G

Variant names:

• chr11-34646624-C-G
• rs369404357
• NM_012153.6:c.283C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012153.6(EHF):​c.283C>G​(p.Arg95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R95W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EHF NM_012153.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29003096).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	NM_012153.6	MANE Select	c.283C>G	p.Arg95Gly	missense	Exon 3 of 9	NP_036285.2
	EHF	NM_001206616.2		c.349C>G	p.Arg117Gly	missense	Exon 3 of 9	NP_001193545.1	Q9NZC4-3
	EHF	NM_001378052.1		c.349C>G	p.Arg117Gly	missense	Exon 3 of 9	NP_001364981.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	ENST00000257831.8	TSL:1 MANE Select	c.283C>G	p.Arg95Gly	missense	Exon 3 of 9	ENSP00000257831.3	Q9NZC4-1
	EHF	ENST00000531794.5	TSL:1	c.349C>G	p.Arg117Gly	missense	Exon 3 of 9	ENSP00000435835.1	Q9NZC4-3
	EHF	ENST00000530286.5	TSL:1	c.283C>G	p.Arg95Gly	missense	Exon 3 of 9	ENSP00000433508.1	Q9NZC4-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Benign	0.34	T
Sift4G	Benign	0.33	T
Polyphen		0.80	P
Vest4		0.46
MutPred		0.59		Loss of helix (P = 0.0626)
MVP		0.43
MPC		1.1
ClinPred		0.68	D
GERP RS		0.99
Varity_R		0.23
gMVP		0.37
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs369404357; hg19: chr11-34668171;