rs1529874

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004826.4(ECEL1):c.982C>T(p.His328Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.981 in 1,613,732 control chromosomes in the GnomAD database, including 777,294 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71002 hom., cov: 33)

Exomes 𝑓: 0.98 ( 706292 hom. )

Consequence

ECEL1
NM_004826.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.11

Publications

33 publications found

Variant links:

Genes affected

ECEL1 (HGNC:3147): (endothelin converting enzyme like 1) This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ECEL1 Gene-Disease associations (from GenCC):

distal arthrogryposis type 5D
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ECEL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.4063277E-7).

BP6

Variant 2-232484878-G-A is Benign according to our data. Variant chr2-232484878-G-A is described in ClinVar as Benign. ClinVar VariationId is 128957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4 link	c.982C>T	p.His328Tyr	missense_variant	Exon 5 of 18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2 link	c.982C>T	p.His328Tyr	missense_variant	Exon 5 of 18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ECEL1	ENST00000304546.6 link	c.982C>T	p.His328Tyr	missense_variant	Exon 5 of 18	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1 link	c.982C>T	p.His328Tyr	missense_variant	Exon 4 of 17	1		ENSP00000386333.1
ECEL1	ENST00000482346.1 link	n.1293C>T		non_coding_transcript_exon_variant	Exon 4 of 17	2

Frequencies

GnomAD3 genomes

AF:

0.965

AC:

146833

AN:

152116

Hom.:

70952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.992

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.984

Gnomad OTH

AF:

0.972

GnomAD2 exomes

AF:

0.985

AC:

247314

AN:

251176

AF XY:

0.986

show subpopulations

Gnomad AFR exome

AF:

0.905

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.991

Gnomad NFE exome

AF:

0.986

Gnomad OTH exome

AF:

0.986

GnomAD4 exome

AF:

0.983

AC:

1436668

AN:

1461498

Hom.:

706292

Cov.:

AF XY:

0.984

AC XY:

715199

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.905

AC:

30296

AN:

33480

American (AMR)

AF:

0.990

AC:

44269

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

26100

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39700

AN:

39700

South Asian (SAS)

AF:

0.996

AC:

85893

AN:

86258

European-Finnish (FIN)

AF:

0.991

AC:

52560

AN:

53060

Middle Eastern (MID)

AF:

0.988

AC:

5699

AN:

5768

European-Non Finnish (NFE)

AF:

0.983

AC:

1092896

AN:

1111984

Other (OTH)

AF:

0.981

AC:

59255

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1520

3039

4559

6078

7598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21658

43316

64974

86632

108290

<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:

0.965

AC:

146940

AN:

152234

Hom.:

71002

Cov.:

AF XY:

0.968

AC XY:

72003

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.909

AC:

37747

AN:

41506

American (AMR)

AF:

0.984

AC:

15054

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3466

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5162

AN:

5162

South Asian (SAS)

AF:

0.997

AC:

4819

AN:

4832

European-Finnish (FIN)

AF:

0.992

AC:

10544

AN:

10624

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.984

AC:

66926

AN:

68012

Other (OTH)

AF:

0.972

AC:

2055

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

254

508

762

1016

1270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.978

Hom.:

161224

Bravo

AF:

0.961

TwinsUK

AF:

0.981

AC:

3637

ALSPAC

AF:

0.982

AC:

3786

ESP6500AA

AF:

0.904

AC:

3985

ESP6500EA

AF:

0.985

AC:

8475

ExAC

AF:

0.983

AC:

119367

Asia WGS

AF:

0.994

AC:

3457

AN:

3478

EpiCase

AF:

0.985

EpiControl

AF:

0.986

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Distal arthrogryposis type 5D

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

N;N

PhyloP100

4.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.25

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.17

MPC

0.16

ClinPred

0.0054

GERP RS

4.9

Varity_R

0.060

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over