rs212528

Variant names:

• chr1-21259168-T-C
• rs212528
• NM_001397.3:c.616-329A>G

Variant summary

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

The NM_001397.3(ECE1):​c.616-329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,188 control chromosomes in the GnomAD database, including 1,130 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 0.12 (1130 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001397.3	c.616-329A>G		intron_variant	Intron 5 of 18	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.616-329A>G		intron_variant	Intron 5 of 18	1	NM_001397.3	ENSP00000364028.6

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18303 AN: 152070 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18335 AN: 152188 Hom.: 1130 Cov.: 32 AF XY: 0.122 AC XY: 9100 AN XY: 74416

African (AFR) AF: 0.108 AC: 4471 AN: 41534

American (AMR) AF: 0.103 AC: 1576 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3470

East Asian (EAS) AF: 0.174 AC: 901 AN: 5172

South Asian (SAS) AF: 0.181 AC: 875 AN: 4830

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8152 AN: 68004

Other (OTH) AF: 0.109 AC: 230 AN: 2112

Alfa AF: 0.120 Hom.: 179

Bravo AF: 0.113

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.9
DANN	Benign	0.32
PhyloP100		1.2
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: rs212528; hg19: chr1-21585661; COSMIC: COSV51662620; COSMIC: COSV51662620;