Variant chr3-184278307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001100121.2(ECE2):c.744T>C(p.Val248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,942 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

ECE2
NM_001100121.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ECE2 links:

EEF1AKMT4-ECE2 (HGNC:):

EEF1AKMT4-ECE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-184278307-T-C is Benign according to our data. Variant chr3-184278307-T-C is described in ClinVar as [Benign]. Clinvar id is 780899.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1628/152234) while in subpopulation AFR AF= 0.0379 (1575/41520). AF 95% confidence interval is 0.0364. There are 27 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ECE2	NM_001100121.2 linkuse as main transcript	c.744T>C	p.Val248=	synonymous_variant	6/19	ENST00000404464.8
EEF1AKMT4-ECE2	NM_014693.4 linkuse as main transcript	c.1098T>C	p.Val366=	synonymous_variant	6/19
ECE2	NM_001100120.2 linkuse as main transcript	c.882T>C	p.Val294=	synonymous_variant	6/19
ECE2	NM_001037324.3 linkuse as main transcript	c.657T>C	p.Val219=	synonymous_variant	5/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE2	ENST00000404464.8 linkuse as main transcript	c.744T>C	p.Val248=	synonymous_variant	6/19	1	NM_001100121.2	P1	P0DPD6-2

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1623

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00264

AC:

662

AN:

250730

Hom.:

AF XY:

0.00179

AC XY:

243

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00111

AC:

1628

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

699

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.0107

AC:

1628

AN:

152234

Hom.:

Cov.:

AF XY:

0.00998

AC XY:

743

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00562

Hom.:

Bravo

AF:

0.0115

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

Invitae

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.8

DANN

Benign

0.66

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

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