chr11-34658506-G-A

Variant names:

• chr11-34658506-G-A
• rs3818514
• NM_012153.6:c.608-27G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000257831.8(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 ENST00000257831.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 9 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 -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000257831.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	NM_012153.6	MANE Select	c.608-27G>A		intron	N/A	NP_036285.2
	EHF	NM_001206616.2		c.674-27G>A		intron	N/A	NP_001193545.1
	EHF	NM_001378052.1		c.671-27G>A		intron	N/A	NP_001364981.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHF	ENST00000257831.8	TSL:1 MANE Select	c.608-27G>A		intron	N/A	ENSP00000257831.3
	EHF	ENST00000531794.5	TSL:1	c.674-27G>A		intron	N/A	ENSP00000435835.1
	EHF	ENST00000530286.5	TSL:1	c.608-27G>A		intron	N/A	ENSP00000433508.1

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

GnomAD2 exomes AF: 0.423 AC: 103441 AN: 244430 AF XY: 0.438

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 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

African (AFR) AF: 0.222 AC: 7302 AN: 32830

American (AMR) AF: 0.253 AC: 11059 AN: 43688

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 14085 AN: 25612

East Asian (EAS) AF: 0.143 AC: 5644 AN: 39494

South Asian (SAS) AF: 0.441 AC: 37291 AN: 84494

European-Finnish (FIN) AF: 0.469 AC: 24826 AN: 52956

Middle Eastern (MID) AF: 0.539 AC: 3062 AN: 5676

European-Non Finnish (NFE) AF: 0.535 AC: 588447 AN: 1100538

Other (OTH) AF: 0.476 AC: 28382 AN: 59662

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

African (AFR) AF: 0.237 AC: 9805 AN: 41438

American (AMR) AF: 0.351 AC: 5364 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1866 AN: 3464

East Asian (EAS) AF: 0.129 AC: 668 AN: 5164

South Asian (SAS) AF: 0.420 AC: 2013 AN: 4798

European-Finnish (FIN) AF: 0.463 AC: 4879 AN: 10530

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36243 AN: 67934

Other (OTH) AF: 0.448 AC: 942 AN: 2104

Alfa AF: 0.493 Hom.: 76399

Bravo AF: 0.391

Asia WGS AF: 0.223 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.020
DANN	Benign	0.63
PhyloP100		-2.1
BranchPoint Hunter		0.0
Mutation Taster		=100/0	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: rs3818514; hg19: chr11-34680053;