rs212531

Positions:

• chr1-21261785-G-A

Variant summary

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

The ENST00000374893.11(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 ENST00000374893.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3	c.494-1393C>T		intron_variant		ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.494-1393C>T		intron_variant		1	NM_001397.3	ENSP00000364028

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

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.102

Alfa AF: 0.123 Hom.: 690

Bravo AF: 0.108

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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