rs213032

Positions:

• chr1-21328242-T-C

Variant summary

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

The NM_001113348.2(ECE1):​c.3+17134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,114 control chromosomes in the GnomAD database, including 13,359 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 0.38 (13359 hom., cov: 32)
• Consequence: ECE1 NM_001113348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001113348.2	c.3+17134A>G		intron_variant			NP_001106819.1
ECE1	XM_011540872.3	c.75+964A>G		intron_variant			XP_011539174.1
ECE1	XM_011540873.3	c.-1+16695A>G		intron_variant			XP_011539175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000415912.6	c.3+17134A>G		intron_variant		1		ENSP00000405088.2
ECE1	ENST00000649812.1	c.3+17134A>G		intron_variant				ENSP00000497333.1
ECE1	ENST00000463334.2	n.201+16695A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57597 AN: 151996 Hom.: 13334 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.379 AC: 57682 AN: 152114 Hom.: 13359 Cov.: 32 AF XY: 0.376 AC XY: 27992 AN XY: 74352

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.358

Alfa AF: 0.275 Hom.: 10003

Bravo AF: 0.395

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs213032; hg19: chr1-21654735;