rs213046

chr1-21291253-A-Cchr1-21291253-A-T

Variant summary

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

The ENST00000415912.6(ECE1):c.4-1097T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,230 control chromosomes in the GnomAD database, including 1,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.11 (1167 hom., cov: 32)
• Consequence: ECE1 ENST00000415912.6 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.00400

Genes affected

ECE1 (HGNC:3146): (endothelin converting enzyme 1) The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECE1	NM_001113348.2	c.4-1097T>G		intron_variant
ECE1	XM_006710398.3	c.1-1097T>G		intron_variant
ECE1	XM_011540872.3	c.76-1097T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE1	ENST00000415912.6	c.4-1097T>G		intron_variant		1		P1
ECE1	ENST00000481130.6	c.10-1097T>G		intron_variant		4
ECE1	ENST00000527991.2	c.1-1097T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16072 AN: 152112 Hom.: 1170 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0926

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16081 AN: 152230 Hom.: 1167 Cov.: 32 AF XY: 0.112 AC XY: 8310 AN XY: 74424

Gnomad4 AFR AF: 0.0818

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.0565 Hom.: 68

Bravo AF: 0.103

Asia WGS AF: 0.286 AC: 991 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypertension, essential, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 15, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.5
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs213046; hg19: chr1-21617746; COSMIC: COSV51662787; COSMIC: COSV51662787;