rs3026868

Positions:

• chr1-21271643-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001397.3(ECE1):​c.493+1056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,106 control chromosomes in the GnomAD database, including 552 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 0.073 (552 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECE1	NM_001397.3	c.493+1056G>A		intron_variant		ENST00000374893.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE1	ENST00000374893.11	c.493+1056G>A		intron_variant		1	NM_001397.3

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11104 AN: 151986 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0730 AC: 11099 AN: 152106 Hom.: 552 Cov.: 32 AF XY: 0.0713 AC XY: 5300 AN XY: 74338

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0541

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.102 Hom.: 535

Bravo AF: 0.0687

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.64

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: rs3026868; hg19: chr1-21598136;