Genetic Variant NM_001397.3:c.*92C>A (chr1-21219863-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001397.3(ECE1):c.*92C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,549,356 control chromosomes in the GnomAD database, including 802 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 0.023 ( 76 hom., cov: 32)

Exomes 𝑓: 0.030 ( 726 hom. )

Consequence

ECE1
NM_001397.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.236

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

essential hypertension, genetic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ECE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0234 (3565/152344) while in subpopulation NFE AF = 0.031 (2106/68022). AF 95% confidence interval is 0.0299. There are 76 homozygotes in GnomAd4. There are 1822 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 76 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001397.3 link	c.*92C>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000374893.11	NP_001388.1	P42892-1A1PUP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11 link	c.*92C>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_001397.3	ENSP00000364028.6		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3569

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00682

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0298

AC:

41626

AN:

1397012

Hom.:

726

Cov.:

AF XY:

0.0292

AC XY:

20289

AN XY:

694334

show subpopulations

African (AFR)

AF:

0.00368

AC:

118

AN:

32096

American (AMR)

AF:

0.0115

AC:

456

AN:

39686

Ashkenazi Jewish (ASJ)

AF:

0.0333

AC:

844

AN:

25344

East Asian (EAS)

AF:

0.00

AC:

AN:

38118

South Asian (SAS)

AF:

0.00819

AC:

673

AN:

82168

European-Finnish (FIN)

AF:

0.0620

AC:

3121

AN:

50332

Middle Eastern (MID)

AF:

0.0159

AC:

AN:

4092

European-Non Finnish (NFE)

AF:

0.0326

AC:

34805

AN:

1067274

Other (OTH)

AF:

0.0267

AC:

1544

AN:

57902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1941

3883

5824

7766

9707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1264

2528

3792

5056

6320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0234

AC:

3565

AN:

152344

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1822

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00611

AC:

254

AN:

41584

American (AMR)

AF:

0.0174

AC:

266

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00683

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0657

AC:

698

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0310

AC:

2106

AN:

68022

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

175

351

526

702

877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0273

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.6

(source)

DANN

Benign

0.78

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over