Variant chr1-150509420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004425.4(ECM1):c.71-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,178,012 control chromosomes in the GnomAD database, including 439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 107 hom., cov: 32)

Exomes 𝑓: 0.023 ( 332 hom. )

Consequence

ECM1
NM_004425.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.475

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-150509420-C-T is Benign according to our data. Variant chr1-150509420-C-T is described in ClinVar as [Benign]. Clinvar id is 1230177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ECM1	NM_004425.4 linkuse as main transcript	c.71-111C>T	intron_variant	ENST00000369047.9
ECM1	NM_001202858.2 linkuse as main transcript	c.71-111C>T	intron_variant
ECM1	NM_022664.3 linkuse as main transcript	c.71-111C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9 linkuse as main transcript	c.71-111C>T		intron_variant		1	NM_004425.4	P1	Q16610-1

Frequencies

GnomAD3 genomes

AF:

0.0328

AC:

4982

AN:

152076

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.00734

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0249

Gnomad OTH

AF:

0.0392

GnomAD4 exome

AF:

0.0227

AC:

23278

AN:

1025818

Hom.:

332

Cov.:

AF XY:

0.0221

AC XY:

11686

AN XY:

528302

show subpopulations

Gnomad4 AFR exome

AF:

0.0596

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0500

Gnomad4 EAS exome

AF:

0.0000810

Gnomad4 SAS exome

AF:

0.00839

Gnomad4 FIN exome

AF:

0.00820

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0327

AC:

4979

AN:

152194

Hom.:

107

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0553

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00994

Gnomad4 FIN

AF:

0.00734

Gnomad4 NFE

AF:

0.0249

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0356

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

DANN

Benign

0.41

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

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