rs3818514

Positions:

• chr11-34658506-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012153.6(EHF):​c.608-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,596,852 control chromosomes in the GnomAD database, including 201,123 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.41 (14523 hom., cov: 31)
  • Exomes 𝑓: 0.50 (186600 hom.)
• Consequence: EHF NM_012153.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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 -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHF	NM_012153.6	c.608-27G>A		intron_variant		ENST00000257831.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHF	ENST00000257831.8	c.608-27G>A		intron_variant		1	NM_012153.6	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62585 AN: 151784 Hom.: 14518 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.453

GnomAD3 exomes AF: 0.423 AC: 103441 AN: 244430 Hom.: 24620 AF XY: 0.438 AC XY: 57939 AN XY: 132152

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.120

Gnomad SAS exome AF: 0.436

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.460

GnomAD4 exome AF: 0.498 AC: 720098 AN: 1444950 Hom.: 186600 Cov.: 29 AF XY: 0.499 AC XY: 358310 AN XY: 717714

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.412 AC: 62599 AN: 151902 Hom.: 14523 Cov.: 31 AF XY: 0.407 AC XY: 30214 AN XY: 74222

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.448

Alfa AF: 0.510 Hom.: 35458

Bravo AF: 0.391

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.020
DANN	Benign	0.63
BranchPoint Hunter		0.0

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: rs3818514; hg19: chr11-34680053;