rs213045

Variant names:

• chr1-21290752-G-T
• rs213045
• ENST00000415912.6:c.4-596C>A

Variant summary

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

The NM_001113348.2(ECE1):​c.4-596C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,094 control chromosomes in the GnomAD database, including 18,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.44 (18573 hom., cov: 32)
• Consequence: ECE1 NM_001113348.2 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.399

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 (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001113348.2	c.4-596C>A		intron_variant	Intron 1 of 18		NP_001106819.1
ECE1	XM_011540872.3	c.76-596C>A		intron_variant	Intron 1 of 18		XP_011539174.1
ECE1	XM_006710398.3	c.1-596C>A		intron_variant	Intron 1 of 18		XP_006710461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000415912.6	c.4-596C>A		intron_variant	Intron 1 of 18	1		ENSP00000405088.2
ECE1	ENST00000649812.1	c.4-596C>A		intron_variant	Intron 1 of 19			ENSP00000497333.1
ECE1	ENST00000481130.6	c.10-596C>A		intron_variant	Intron 1 of 3	4		ENSP00000436633.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66527 AN: 151976 Hom.: 18530 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.438 AC: 66626 AN: 152094 Hom.: 18573 Cov.: 32 AF XY: 0.435 AC XY: 32342 AN XY: 74342

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.418

Alfa AF: 0.339 Hom.: 5886

Bravo AF: 0.459

Asia WGS AF: 0.430 AC: 1490 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypertension, essential, susceptibility to Other:1

Feb 15, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs213045; hg19: chr1-21617245;