chr1-150509669-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004425.4(ECM1):c.130G>A(p.Ala44Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00887 in 1,613,572 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 81 hom. )

Consequence

ECM1
NM_004425.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.29

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013135403).

BP6

Variant 1-150509669-G-A is Benign according to our data. Variant chr1-150509669-G-A is described in ClinVar as [Benign]. Clinvar id is 777102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150509669-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00785 (1193/152012) while in subpopulation NFE AF= 0.0129 (874/67934). AF 95% confidence interval is 0.0122. There are 7 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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.130G>A	p.Ala44Thr	missense_variant	Exon 3 of 10	ENST00000369047.9	NP_004416.2	Q16610-1A0A140VJI7
ECM1	NM_001202858.2 link	c.130G>A	p.Ala44Thr	missense_variant	Exon 3 of 10		NP_001189787.1	Q16610-4
ECM1	NM_022664.3 link	c.130G>A	p.Ala44Thr	missense_variant	Exon 3 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.130G>A	p.Ala44Thr	missense_variant	Exon 3 of 10	1	NM_004425.4	ENSP00000358043.4		Q16610-1

Frequencies

GnomAD3 genomes

AF:

0.00785

AC:

1193

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00172

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00721

AC:

1813

AN:

251434

Hom.:

AF XY:

0.00720

AC XY:

978

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00201

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00933

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00880

GnomAD4 exome

AF:

0.00898

AC:

13122

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

6473

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.00383

Gnomad4 EAS exome

AF:

0.000705

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.00897

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.00785

AC:

1193

AN:

152012

Hom.:

Cov.:

AF XY:

0.00749

AC XY:

557

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00723

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.00749

AC:

909

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0100

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ECM1: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ECM1-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

0.057

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.83

MVP

0.96

MPC

0.51

ClinPred

0.030

GERP RS

4.3

Varity_R

0.40

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over