rs213032

Variant names:

• chr1-21328242-T-C
• rs213032
• ENST00000415912.6:c.3+17134A>G

Variant summary

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

The NM_001113348.2(ECE1):​c.3+17134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,114 control chromosomes in the GnomAD database, including 13,359 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 0.38 (13359 hom., cov: 32)
• Consequence: ECE1 NM_001113348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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.3+17134A>G		intron	N/A	NP_001106819.1	P42892-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000415912.6	TSL:1	c.3+17134A>G		intron	N/A	ENSP00000405088.2	P42892-3
	ECE1	ENST00000649812.1		c.3+17134A>G		intron	N/A	ENSP00000497333.1	A0A3B3ISF9
	ECE1	ENST00000463334.2	TSL:3	n.201+16695A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57597 AN: 151996 Hom.: 13334 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.379 AC: 57682 AN: 152114 Hom.: 13359 Cov.: 32 AF XY: 0.376 AC XY: 27992 AN XY: 74352

African (AFR) AF: 0.655 AC: 27198 AN: 41496

American (AMR) AF: 0.303 AC: 4633 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1066 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5168

South Asian (SAS) AF: 0.386 AC: 1859 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2592 AN: 10586

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17350 AN: 67980

Other (OTH) AF: 0.358 AC: 755 AN: 2110

Alfa AF: 0.295 Hom.: 28444

Bravo AF: 0.395

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-2.1
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: rs213032; hg19: chr1-21654735;