rs212522

Variant names:

• chr1-21255932-C-T
• rs212522
• NM_001397.3:c.1020+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001397.3(ECE1):​c.1020+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,326 control chromosomes in the GnomAD database, including 13,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (947 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12314 hom.)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.60
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-21255932-C-T is Benign according to our data. Variant chr1-21255932-C-T is described in ClinVar as Benign. ClinVar VariationId is 258078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 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.1020+15G>A		intron	N/A	NP_001388.1
	ECE1	NM_001113349.2		c.1011+15G>A		intron	N/A	NP_001106820.1
	ECE1	NM_001113347.2		c.984+15G>A		intron	N/A	NP_001106818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000374893.11	TSL:1 MANE Select	c.1020+15G>A		intron	N/A	ENSP00000364028.6
	ECE1	ENST00000264205.10	TSL:1	c.1011+15G>A		intron	N/A	ENSP00000264205.6
	ECE1	ENST00000357071.8	TSL:1	c.984+15G>A		intron	N/A	ENSP00000349581.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15552 AN: 152180 Hom.: 946 Cov.: 33

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0903

GnomAD2 exomes AF: 0.127 AC: 31899 AN: 250756 AF XY: 0.130

Gnomad AFR exome AF: 0.0420

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.0902

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.126 AC: 183671 AN: 1461028 Hom.: 12314 Cov.: 32 AF XY: 0.127 AC XY: 92378 AN XY: 726774

African (AFR) AF: 0.0419 AC: 1404 AN: 33476

American (AMR) AF: 0.117 AC: 5243 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 2423 AN: 26132

East Asian (EAS) AF: 0.185 AC: 7350 AN: 39698

South Asian (SAS) AF: 0.170 AC: 14684 AN: 86228

European-Finnish (FIN) AF: 0.158 AC: 8370 AN: 52966

Middle Eastern (MID) AF: 0.0794 AC: 458 AN: 5766

European-Non Finnish (NFE) AF: 0.123 AC: 136432 AN: 1111674

Other (OTH) AF: 0.121 AC: 7307 AN: 60372

GnomAD4 genome AF: 0.102 AC: 15582 AN: 152298 Hom.: 947 Cov.: 33 AF XY: 0.105 AC XY: 7823 AN XY: 74468

African (AFR) AF: 0.0452 AC: 1877 AN: 41566

American (AMR) AF: 0.0943 AC: 1442 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.169 AC: 875 AN: 5188

South Asian (SAS) AF: 0.175 AC: 843 AN: 4826

European-Finnish (FIN) AF: 0.166 AC: 1763 AN: 10602

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8156 AN: 68026

Other (OTH) AF: 0.0922 AC: 195 AN: 2116

Alfa AF: 0.109 Hom.: 1287

Bravo AF: 0.0917

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.43
PhyloP100		-2.6
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: rs212522; hg19: chr1-21582425; COSMIC: COSV51661842; COSMIC: COSV51661842;