chr1-21258521-C-T

Variant names:

• chr1-21258521-C-T
• rs212527
• NM_001397.3:c.762+172G>A

Variant summary

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

The NM_001397.3(ECE1):​c.762+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,188 control chromosomes in the GnomAD database, including 1,109 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 (1109 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 3 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 = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001397.3	c.762+172G>A		intron_variant	Intron 6 of 18	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.762+172G>A		intron_variant	Intron 6 of 18	1	NM_001397.3	ENSP00000364028.6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18119 AN: 152070 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.119 AC: 18150 AN: 152188 Hom.: 1109 Cov.: 32 AF XY: 0.121 AC XY: 9012 AN XY: 74412

African (AFR) AF: 0.106 AC: 4418 AN: 41518

American (AMR) AF: 0.100 AC: 1534 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3468

East Asian (EAS) AF: 0.167 AC: 863 AN: 5164

South Asian (SAS) AF: 0.177 AC: 855 AN: 4824

European-Finnish (FIN) AF: 0.159 AC: 1689 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8131 AN: 68012

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.109 Hom.: 1240

Bravo AF: 0.112

Asia WGS AF: 0.159 AC: 554 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	1.0
DANN	Benign	0.63
PhyloP100		-0.35
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: rs212527; hg19: chr1-21585014; COSMIC: COSV51662611; COSMIC: COSV51662611;