rs3026905

chr1-21225121-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001397.3(ECE1):c.2040+129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,266,276 control chromosomes in the GnomAD database, including 768 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 0.027 (86 hom., cov: 32)
  • Exomes 𝑓: 0.032 (682 hom.)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0273 (4154/152270) while in subpopulation NFE AF= 0.0342 (2326/68020). AF 95% confidence interval is 0.033. There are 86 homozygotes in gnomad4. There are 2104 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 4155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECE1	NM_001397.3	c.2040+129C>T		intron_variant		ENST00000374893.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE1	ENST00000374893.11	c.2040+129C>T		intron_variant		1	NM_001397.3

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4155 AN: 152152 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0264

GnomAD4 exome AF: 0.0322 AC: 35878 AN: 1114006 Hom.: 682 AF XY: 0.0316 AC XY: 17549 AN XY: 555062

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0342

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.0609

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0309

GnomAD4 genome AF: 0.0273 AC: 4154 AN: 152270 Hom.: 86 Cov.: 32 AF XY: 0.0283 AC XY: 2104 AN XY: 74448

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0663

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0306 Hom.: 16

Bravo AF: 0.0240

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.12
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs3026905; hg19: chr1-21551614;