rs212531

Variant names:

• chr1-21261785-G-A
• rs212531
• NM_001397.3:c.494-1393C>T

Variant summary

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

The NM_001397.3(ECE1):​c.494-1393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,216 control chromosomes in the GnomAD database, including 1,084 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 (1084 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	NM_001397.3	MANE Select	c.494-1393C>T		intron	N/A	NP_001388.1
	ECE1	NM_001113349.2		c.485-1393C>T		intron	N/A	NP_001106820.1
	ECE1	NM_001113347.2		c.458-1393C>T		intron	N/A	NP_001106818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000374893.11	TSL:1 MANE Select	c.494-1393C>T		intron	N/A	ENSP00000364028.6
	ECE1	ENST00000264205.10	TSL:1	c.485-1393C>T		intron	N/A	ENSP00000264205.6
	ECE1	ENST00000357071.8	TSL:1	c.458-1393C>T		intron	N/A	ENSP00000349581.4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17637 AN: 152098 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.116 AC: 17668 AN: 152216 Hom.: 1084 Cov.: 32 AF XY: 0.118 AC XY: 8791 AN XY: 74412

African (AFR) AF: 0.0935 AC: 3885 AN: 41544

American (AMR) AF: 0.0976 AC: 1492 AN: 15288

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

East Asian (EAS) AF: 0.183 AC: 942 AN: 5160

South Asian (SAS) AF: 0.181 AC: 873 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1683 AN: 10600

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8143 AN: 68018

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.122 Hom.: 986

Bravo AF: 0.108

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.77
PhyloP100		0.20
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: rs212531; hg19: chr1-21588278; COSMIC: COSV51662662; COSMIC: COSV51662662;