rs213046

Variant names:

• chr1-21291253-A-C
• rs213046
• ENST00000415912.6:c.4-1097T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-21291253-A-C
• chr1-21291253-A-T

Variant summary

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

The NM_001113348.2(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 NM_001113348.2 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.00400
• Publications: 8 publications found

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]

ECE1 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113348.2. 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
	ECE1	NM_001113348.2		c.4-1097T>G		intron	N/A	NP_001106819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000415912.6	TSL:1	c.4-1097T>G		intron	N/A	ENSP00000405088.2
	ECE1	ENST00000649812.1		c.4-1097T>G		intron	N/A	ENSP00000497333.1
	ECE1	ENST00000481130.6	TSL:4	c.10-1097T>G		intron	N/A	ENSP00000436633.1

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

African (AFR) AF: 0.0818 AC: 3401 AN: 41560

American (AMR) AF: 0.114 AC: 1744 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2208 AN: 5158

South Asian (SAS) AF: 0.189 AC: 911 AN: 4814

European-Finnish (FIN) AF: 0.154 AC: 1636 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5806 AN: 68008

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.0787 Hom.: 247

Bravo AF: 0.103

Asia WGS AF: 0.286 AC: 991 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Hypertension, essential, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.5
DANN	Benign	0.81
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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