chr1-21247229-G-A

Variant names:

• chr1-21247229-G-A
• rs2229450
• NM_001397.3:c.1155C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001397.3(ECE1):​c.1155C>T​(p.Thr385Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,978 control chromosomes in the GnomAD database, including 51,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3674 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47655 hom.)
• Consequence: ECE1 NM_001397.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.05
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-21247229-G-A is Benign according to our data. Variant chr1-21247229-G-A is described in ClinVar as Benign. ClinVar VariationId is 258080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	NM_001397.3	MANE Select	c.1155C>T	p.Thr385Thr	synonymous	Exon 9 of 19	NP_001388.1	P42892-1
	ECE1	NM_001113349.2		c.1146C>T	p.Thr382Thr	synonymous	Exon 8 of 18	NP_001106820.1	P42892-4
	ECE1	NM_001113347.2		c.1119C>T	p.Thr373Thr	synonymous	Exon 7 of 17	NP_001106818.1	P42892-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000374893.11	TSL:1 MANE Select	c.1155C>T	p.Thr385Thr	synonymous	Exon 9 of 19	ENSP00000364028.6	P42892-1
	ECE1	ENST00000264205.10	TSL:1	c.1146C>T	p.Thr382Thr	synonymous	Exon 8 of 18	ENSP00000264205.6	P42892-4
	ECE1	ENST00000357071.8	TSL:1	c.1119C>T	p.Thr373Thr	synonymous	Exon 7 of 17	ENSP00000349581.4	P42892-2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29880 AN: 152084 Hom.: 3676 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.222 AC: 55757 AN: 251464 AF XY: 0.224

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.250 AC: 365674 AN: 1461778 Hom.: 47655 Cov.: 37 AF XY: 0.248 AC XY: 180415 AN XY: 727180

African (AFR) AF: 0.0474 AC: 1586 AN: 33480

American (AMR) AF: 0.216 AC: 9652 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5598 AN: 26134

East Asian (EAS) AF: 0.145 AC: 5745 AN: 39694

South Asian (SAS) AF: 0.175 AC: 15062 AN: 86256

European-Finnish (FIN) AF: 0.259 AC: 13854 AN: 53418

Middle Eastern (MID) AF: 0.247 AC: 1425 AN: 5764

European-Non Finnish (NFE) AF: 0.269 AC: 299063 AN: 1111914

Other (OTH) AF: 0.227 AC: 13689 AN: 60394

GnomAD4 genome AF: 0.196 AC: 29879 AN: 152200 Hom.: 3674 Cov.: 32 AF XY: 0.193 AC XY: 14375 AN XY: 74398

African (AFR) AF: 0.0521 AC: 2166 AN: 41554

American (AMR) AF: 0.237 AC: 3622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.133 AC: 687 AN: 5172

South Asian (SAS) AF: 0.158 AC: 763 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2832 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18354 AN: 68000

Other (OTH) AF: 0.206 AC: 436 AN: 2114

Alfa AF: 0.238 Hom.: 2409

Bravo AF: 0.188

Asia WGS AF: 0.136 AC: 476 AN: 3478

EpiCase AF: 0.255

EpiControl AF: 0.270

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.092
DANN	Benign	0.44
PhyloP100		-6.1
Mutation Taster		=99/1	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: rs2229450; hg19: chr1-21573722; COSMIC: COSV51668495;