rs13294

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_004425.4(ECM1):c.1243G>A(p.Gly415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,613,130 control chromosomes in the GnomAD database, including 121,478 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9096 hom., cov: 28)

Exomes 𝑓: 0.39 ( 112382 hom. )

Consequence

ECM1
NM_004425.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.878

Publications

85 publications found

Variant links:

Genes affected

ECM1 (HGNC:3153): (extracellular matrix protein 1) This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ECM1 Gene-Disease associations (from GenCC):

lipoid proteinosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet

ECM1 links:

ENSG00000307101 (HGNC:):

ENSG00000307101 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=0.0036849082).

BP6

Variant 1-150512511-G-A is Benign according to our data. Variant chr1-150512511-G-A is described in ClinVar as Benign. ClinVar VariationId is 1255367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ECM1	NM_004425.4 link	c.1243G>A	p.Gly415Ser	missense_variant	Exon 8 of 10	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2 link	c.1324G>A	p.Gly442Ser	missense_variant	Exon 8 of 10		NP_001189787.1
ECM1	NM_022664.3 link	c.868G>A	p.Gly290Ser	missense_variant	Exon 7 of 9		NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9 link	c.1243G>A	p.Gly415Ser	missense_variant	Exon 8 of 10	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50422

AN:

151166

Hom.:

9088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.352

AC:

88524

AN:

251444

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.387

AC:

565697

AN:

1461846

Hom.:

112382

Cov.:

AF XY:

0.388

AC XY:

282325

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.194

AC:

6491

AN:

33480

American (AMR)

AF:

0.233

AC:

10403

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

12993

AN:

26134

East Asian (EAS)

AF:

0.260

AC:

10339

AN:

39700

South Asian (SAS)

AF:

0.341

AC:

29415

AN:

86254

European-Finnish (FIN)

AF:

0.418

AC:

22320

AN:

53418

Middle Eastern (MID)

AF:

0.440

AC:

2539

AN:

5768

European-Non Finnish (NFE)

AF:

0.403

AC:

447990

AN:

1111974

Other (OTH)

AF:

0.384

AC:

23207

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

24135

48270

72404

96539

120674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13574

27148

40722

54296

67870

<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:

0.333

AC:

50448

AN:

151284

Hom.:

9096

Cov.:

AF XY:

0.332

AC XY:

24510

AN XY:

73846

show subpopulations

African (AFR)

AF:

0.204

AC:

8386

AN:

41178

American (AMR)

AF:

0.293

AC:

4429

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1760

AN:

3464

East Asian (EAS)

AF:

0.246

AC:

1262

AN:

5126

South Asian (SAS)

AF:

0.330

AC:

1580

AN:

4784

European-Finnish (FIN)

AF:

0.410

AC:

4293

AN:

10462

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.405

AC:

27471

AN:

67840

Other (OTH)

AF:

0.363

AC:

761

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1591

3183

4774

6366

7957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.385

Hom.:

54134

Bravo

AF:

0.317

TwinsUK

AF:

0.406

AC:

1504

ALSPAC

AF:

0.389

AC:

1500

ESP6500AA

AF:

0.208

AC:

917

ESP6500EA

AF:

0.411

AC:

3534

ExAC

AF:

0.353

AC:

42837

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.412

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lipid proteinosis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.080

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.47

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

.;N;.

PhyloP100

0.88

PrimateAI

Benign

0.42

PROVEAN

Benign

2.8

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.056

MPC

0.10

ClinPred

0.0030

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.43

Mutation Taster

=98/2

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