rs212528

chr1-21259168-T-C

Variant summary

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

The NM_001397.3(ECE1):c.616-329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,188 control chromosomes in the GnomAD database, including 1,130 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 (1130 hom., cov: 32)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECE1	NM_001397.3	c.616-329A>G		intron_variant		ENST00000374893.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE1	ENST00000374893.11	c.616-329A>G		intron_variant		1	NM_001397.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18303 AN: 152070 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18335 AN: 152188 Hom.: 1130 Cov.: 32 AF XY: 0.122 AC XY: 9100 AN XY: 74416

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.109

Alfa AF: 0.121 Hom.: 179

Bravo AF: 0.113

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	7.9
Dann	Benign	0.32

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: rs212528; hg19: chr1-21585661; COSMIC: COSV51662620; COSMIC: COSV51662620;