Variant 1-21217754-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001397.3(ECE1):c.*2201A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 152,382 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.011 ( 0 hom. )

Consequence

ECE1
NM_001397.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.444

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033914149).

BP6

Variant 1-21217754-T-A is Benign according to our data. Variant chr1-21217754-T-A is described in ClinVar as [Benign]. Clinvar id is 3025059.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2277/152198) while in subpopulation NFE AF= 0.0236 (1607/67986). AF 95% confidence interval is 0.0227. There are 26 homozygotes in gnomad4. There are 1026 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3 linkuse as main transcript	c.*2201A>T		3_prime_UTR_variant	19/19	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11 linkuse as main transcript	c.*2201A>T		3_prime_UTR_variant	19/19	1	NM_001397.3	ENSP00000364028		P42892-1
ECE1	ENST00000415912.6 linkuse as main transcript	c.*2201A>T		3_prime_UTR_variant	19/19	1		ENSP00000405088	P1	P42892-3
ECE1	ENST00000649812.1 linkuse as main transcript	c.2486A>T	p.Glu829Val	missense_variant	20/20			ENSP00000497333

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2278

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00851

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.0109

AC:

AN:

184

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

AN XY:

148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0150

AC:

2277

AN:

152198

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1026

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00376

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00852

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0236

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0159

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0236

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

ECE1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

DANN

Benign

0.51

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0034

MutationTaster

Benign

1.0

GERP RS

1.8

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over