dbSNP rs6750085: ECEL1:c.1507-30G>C (chr2-232483209-C-G) – ACMG Classification: Benign (-20 pts)

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.1507-30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,583,368 control chromosomes in the GnomAD database, including 134,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10580 hom., cov: 33)

Exomes 𝑓: 0.41 ( 123454 hom. )

Consequence

ECEL1
NM_004826.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.391

Publications

7 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

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 (BayesDel_noAF=-0.84).

BP6

Variant 2-232483209-C-G is Benign according to our data. Variant chr2-232483209-C-G is described in ClinVar as Benign. ClinVar VariationId is 1250015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004826.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECEL1	NM_004826.4	MANE Select	c.1507-30G>C		intron	N/A	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.1507-30G>C		intron	N/A	NP_001277716.1	O95672-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ECEL1	ENST00000304546.6	TSL:1 MANE Select	c.1507-30G>C	intron	N/A	ENSP00000302051.1	O95672-1
ECEL1	ENST00000409941.1	TSL:1	c.1507-30G>C	intron	N/A	ENSP00000386333.1	O95672-2
ECEL1	ENST00000862796.1		c.1507-30G>C	intron	N/A	ENSP00000532855.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54671

AN:

151958

Hom.:

10584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.405

GnomAD2 exomes

AF:

0.393

AC:

78109

AN:

199000

AF XY:

0.397

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.445

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.412

AC:

589493

AN:

1431296

Hom.:

123454

Cov.:

AF XY:

0.411

AC XY:

291447

AN XY:

709178

show subpopulations

African (AFR)

AF:

0.210

AC:

6932

AN:

33086

American (AMR)

AF:

0.354

AC:

13673

AN:

38616

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

12191

AN:

25580

East Asian (EAS)

AF:

0.279

AC:

10716

AN:

38466

South Asian (SAS)

AF:

0.344

AC:

28484

AN:

82746

European-Finnish (FIN)

AF:

0.418

AC:

21131

AN:

50580

Middle Eastern (MID)

AF:

0.428

AC:

2450

AN:

5730

European-Non Finnish (NFE)

AF:

0.429

AC:

470199

AN:

1097198

Other (OTH)

AF:

0.400

AC:

23717

AN:

59294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

20561

41122

61682

82243

102804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14304

28608

42912

57216

71520

<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:

0.359

AC:

54663

AN:

152072

Hom.:

10580

Cov.:

AF XY:

0.360

AC XY:

26777

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.216

AC:

8968

AN:

41520

American (AMR)

AF:

0.359

AC:

5485

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1712

AN:

3472

East Asian (EAS)

AF:

0.262

AC:

1345

AN:

5142

South Asian (SAS)

AF:

0.346

AC:

1671

AN:

4824

European-Finnish (FIN)

AF:

0.428

AC:

4522

AN:

10572

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.434

AC:

29480

AN:

67946

Other (OTH)

AF:

0.402

AC:

848

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1763

3527

5290

7054

8817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.406

Hom.:

2384

Bravo

AF:

0.350

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Distal arthrogryposis type 5D (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

(source)

DANN

Benign

0.59

PhyloP100

-0.39

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over