rs286891

Variant names:

• chr11-34658853-T-A
• rs286891
• NM_012153.6:c.825T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012153.6(EHF):​c.825T>A​(p.Ile275Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,612,116 control chromosomes in the GnomAD database, including 11,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (953 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10603 hom.)
• Consequence: EHF NM_012153.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 15 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.048 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

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.825T>A	p.Ile275Ile	synonymous	Exon 9 of 9	NP_036285.2
	EHF	NM_001206616.2		c.891T>A	p.Ile297Ile	synonymous	Exon 9 of 9	NP_001193545.1	Q9NZC4-3
	EHF	NM_001378052.1		c.888T>A	p.Ile296Ile	synonymous	Exon 9 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.825T>A	p.Ile275Ile	synonymous	Exon 9 of 9	ENSP00000257831.3	Q9NZC4-1
	EHF	ENST00000531794.5	TSL:1	c.891T>A	p.Ile297Ile	synonymous	Exon 9 of 9	ENSP00000435835.1	Q9NZC4-3
	EHF	ENST00000530286.5	TSL:1	c.825T>A	p.Ile275Ile	synonymous	Exon 9 of 9	ENSP00000433508.1	Q9NZC4-1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15728 AN: 152024 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0918

GnomAD2 exomes AF: 0.123 AC: 30690 AN: 249672 AF XY: 0.130

Gnomad AFR exome AF: 0.0612

Gnomad AMR exome AF: 0.0679

Gnomad ASJ exome AF: 0.0669

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.113 AC: 164775 AN: 1459974 Hom.: 10603 Cov.: 32 AF XY: 0.117 AC XY: 85145 AN XY: 726230

African (AFR) AF: 0.0557 AC: 1859 AN: 33356

American (AMR) AF: 0.0701 AC: 3117 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1682 AN: 26086

East Asian (EAS) AF: 0.112 AC: 4454 AN: 39652

South Asian (SAS) AF: 0.240 AC: 20626 AN: 85840

European-Finnish (FIN) AF: 0.182 AC: 9691 AN: 53388

Middle Eastern (MID) AF: 0.0942 AC: 543 AN: 5762

European-Non Finnish (NFE) AF: 0.105 AC: 116163 AN: 1111090

Other (OTH) AF: 0.110 AC: 6640 AN: 60322

GnomAD4 genome AF: 0.103 AC: 15725 AN: 152142 Hom.: 953 Cov.: 32 AF XY: 0.109 AC XY: 8123 AN XY: 74370

African (AFR) AF: 0.0610 AC: 2533 AN: 41530

American (AMR) AF: 0.0953 AC: 1455 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.134 AC: 692 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4816

European-Finnish (FIN) AF: 0.193 AC: 2041 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7290 AN: 67992

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0979 Hom.: 249

Bravo AF: 0.0890

Asia WGS AF: 0.183 AC: 637 AN: 3478

EpiCase AF: 0.0994

EpiControl AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.5
DANN	Benign	0.70
PhyloP100		0.048
Mutation Taster		=94/6	polymorphism (auto)

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: rs286891; hg19: chr11-34680400; COSMIC: COSV99140867; COSMIC: COSV99140867;