rs151102225

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004425.4(ECM1):c.1100A>T(p.Asp367Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00987 in 1,612,804 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 7 hom., cov: 27)

Exomes 𝑓: 0.010 ( 92 hom. )

Consequence

ECM1
NM_004425.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.59

Publications

8 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=0.015558243).

BP6

Variant 1-150512368-A-T is Benign according to our data. Variant chr1-150512368-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00728 (1098/150920) while in subpopulation NFE AF = 0.0117 (792/67776). AF 95% confidence interval is 0.011. There are 7 homozygotes in GnomAd4. There are 528 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM1	NM_004425.4 link	c.1100A>T	p.Asp367Val	missense_variant	Exon 8 of 10	ENST00000369047.9	NP_004416.2	Q16610-1A0A140VJI7
ECM1	NM_001202858.2 link	c.1181A>T	p.Asp394Val	missense_variant	Exon 8 of 10		NP_001189787.1	Q16610-4
ECM1	NM_022664.3 link	c.725A>T	p.Asp242Val	missense_variant	Exon 7 of 9		NP_073155.2	Q16610-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9 link	c.1100A>T	p.Asp367Val	missense_variant	Exon 8 of 10	1	NM_004425.4	ENSP00000358043.4		Q16610-1

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

1099

AN:

150802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00612

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00468

Gnomad FIN

AF:

0.00460

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00338

GnomAD2 exomes

AF:

0.00729

AC:

1828

AN:

250644

AF XY:

0.00749

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00332

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00504

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00782

GnomAD4 exome

AF:

0.0101

AC:

14825

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

7221

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00349

AC:

156

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

418

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00599

AC:

517

AN:

86258

European-Finnish (FIN)

AF:

0.00603

AC:

322

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0115

AC:

12809

AN:

1112002

Other (OTH)

AF:

0.00911

AC:

550

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

901

1802

2702

3603

4504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.00728

AC:

1098

AN:

150920

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

528

AN XY:

73632

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41088

American (AMR)

AF:

0.00605

AC:

AN:

15044

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00468

AC:

AN:

4696

European-Finnish (FIN)

AF:

0.00460

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

792

AN:

67776

Other (OTH)

AF:

0.00334

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00943

Hom.:

Bravo

AF:

0.00651

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00773

AC:

939

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00925

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ECM1: BS1, BS2 -

Lipid proteinosis

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

.;D;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Uncertain

-0.084

MutationAssessor

Uncertain

2.3

.;M;.

PhyloP100

2.6

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.4

D;D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.64

MVP

0.95

MPC

0.62

ClinPred

0.032

GERP RS

4.6

Varity_R

0.67

gMVP

0.75

Mutation Taster

=79/21

polymorphism

(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