rs286891

Positions:

• chr11-34658853-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012153.6(EHF):​c.825T>A​(p.Ile275=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHF	NM_012153.6	c.825T>A	p.Ile275=	synonymous_variant	9/9	ENST00000257831.8	NP_036285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHF	ENST00000257831.8	c.825T>A	p.Ile275=	synonymous_variant	9/9	1	NM_012153.6	ENSP00000257831	P1

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

GnomAD3 exomes AF: 0.123 AC: 30690 AN: 249672 Hom.: 2406 AF XY: 0.130 AC XY: 17590 AN XY: 134894

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 SAS exome AF: 0.242

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

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.0701

Gnomad4 ASJ exome AF: 0.0645

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.110

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

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0899

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.5
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

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