chr11-34651570-C-A

Variant names:

• chr11-34651570-C-A
• rs149874101
• NM_012153.6:c.435C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_012153.6(EHF):​c.435C>A​(p.Asp145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,124 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. D145D) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: EHF NM_012153.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.642
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033219814).
• BP6: Variant 11-34651570-C-A is Benign according to our data. Variant chr11-34651570-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3274899.Status of the report is criteria_provided_single_submitter, 1 stars.

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.435C>A	p.Asp145Glu	missense	Exon 5 of 9	NP_036285.2
	EHF	NM_001206616.2		c.501C>A	p.Asp167Glu	missense	Exon 5 of 9	NP_001193545.1	Q9NZC4-3
	EHF	NM_001378052.1		c.501C>A	p.Asp167Glu	missense	Exon 5 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.435C>A	p.Asp145Glu	missense	Exon 5 of 9	ENSP00000257831.3	Q9NZC4-1
	EHF	ENST00000531794.5	TSL:1	c.501C>A	p.Asp167Glu	missense	Exon 5 of 9	ENSP00000435835.1	Q9NZC4-3
	EHF	ENST00000530286.5	TSL:1	c.435C>A	p.Asp145Glu	missense	Exon 5 of 9	ENSP00000433508.1	Q9NZC4-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251270 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74284

African (AFR) AF: 0.0000724 AC: 3 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000165 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.0
DANN	Benign	0.79
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.64
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.062
Sift	Benign	0.62	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.32		Gain of methylation at K144 (P = 0.1208)
MVP		0.32
MPC		0.36
ClinPred		0.023	T
GERP RS		1.3
Varity_R		0.041
gMVP		0.089
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149874101; hg19: chr11-34673117;