rs61731716

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004826.4(ECEL1):c.1995C>T(p.Asn665Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,564,584 control chromosomes in the GnomAD database, including 443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 39 hom., cov: 34)

Exomes 𝑓: 0.022 ( 404 hom. )

Consequence

ECEL1
NM_004826.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.65

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-232481151-G-A is Benign according to our data. Variant chr2-232481151-G-A is described in ClinVar as Benign. ClinVar VariationId is 128953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2385/152346) while in subpopulation NFE AF = 0.0238 (1617/68026). AF 95% confidence interval is 0.0228. There are 39 homozygotes in GnomAd4. There are 1115 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4 link	c.1995C>T	p.Asn665Asn	synonymous_variant	Exon 15 of 18	ENST00000304546.6	NP_004817.2	O95672-1A0A6F7YIA8
ECEL1	NM_001290787.2 link	c.1989C>T	p.Asn663Asn	synonymous_variant	Exon 15 of 18		NP_001277716.1	O95672-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ECEL1	ENST00000304546.6 link	c.1995C>T	p.Asn665Asn	synonymous_variant	Exon 15 of 18	1	NM_004826.4	ENSP00000302051.1	O95672-1
ECEL1	ENST00000409941.1 link	c.1989C>T	p.Asn663Asn	synonymous_variant	Exon 14 of 17	1		ENSP00000386333.1	O95672-2
ECEL1	ENST00000482346.1 link	n.2306C>T		non_coding_transcript_exon_variant	Exon 14 of 17	2
ECEL1	ENST00000411860.5 link	c.235-338C>T		intron_variant	Intron 3 of 5	3		ENSP00000412683.1	H7C3M0

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2386

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0154

AC:

2669

AN:

172986

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.00637

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0154

GnomAD4 exome

AF:

0.0218

AC:

30786

AN:

1412238

Hom.:

404

Cov.:

AF XY:

0.0214

AC XY:

14917

AN XY:

697888

show subpopulations

African (AFR)

AF:

0.00269

AC:

AN:

32354

American (AMR)

AF:

0.00650

AC:

245

AN:

37696

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

662

AN:

25306

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36902

South Asian (SAS)

AF:

0.00954

AC:

764

AN:

80088

European-Finnish (FIN)

AF:

0.0237

AC:

1169

AN:

49296

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0244

AC:

26475

AN:

1086384

Other (OTH)

AF:

0.0225

AC:

1318

AN:

58496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1697

3393

5090

6786

8483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

994

1988

2982

3976

4970

<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:

0.0157

AC:

2385

AN:

152346

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1115

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00392

AC:

163

AN:

41592

American (AMR)

AF:

0.0109

AC:

166

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00869

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0267

AC:

284

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0238

AC:

1617

AN:

68026

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0197

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.5

(source)

DANN

Benign

0.89

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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