1-21231198-G-T

Variant names:

• chr1-21231198-G-T
• rs9287035
• NM_001397.3:c.1670+2360C>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.1670+2360C>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 152,128 control chromosomes in the GnomAD database, including 2,371 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 (2371 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001397.3	c.1670+2360C>A		intron_variant	Intron 14 of 18	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.1670+2360C>A		intron_variant	Intron 14 of 18	1	NM_001397.3	ENSP00000364028.6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18104 AN: 152010 Hom.: 2366 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.119 AC: 18140 AN: 152128 Hom.: 2371 Cov.: 32 AF XY: 0.117 AC XY: 8702 AN XY: 74362

African (AFR) AF: 0.327 AC: 13562 AN: 41450

American (AMR) AF: 0.0628 AC: 959 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4830

European-Finnish (FIN) AF: 0.0663 AC: 702 AN: 10592

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2447 AN: 68014

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0423 Hom.: 138

Bravo AF: 0.129

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.35
PhyloP100		-0.032
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: rs9287035; hg19: chr1-21557691;