Variant chr1-150509506-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_StrongBS1BS2

The NM_004425.4(ECM1):c.71-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,614,010 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 32 hom., cov: 32)

Exomes 𝑓: 0.019 ( 371 hom. )

Consequence

ECM1
NM_004425.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0850

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=-0.84).

BP6

Variant 1-150509506-C-T is Benign according to our data. Variant chr1-150509506-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1206950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0158 (2409/152258) while in subpopulation AMR AF= 0.032 (489/15284). AF 95% confidence interval is 0.0297. There are 32 homozygotes in gnomad4. There are 1135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ECM1	NM_004425.4 linkuse as main transcript	c.71-25C>T	intron_variant	ENST00000369047.9
ECM1	NM_001202858.2 linkuse as main transcript	c.71-25C>T	intron_variant
ECM1	NM_022664.3 linkuse as main transcript	c.71-25C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9 linkuse as main transcript	c.71-25C>T		intron_variant		1	NM_004425.4	P1	Q16610-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2412

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0200

AC:

5025

AN:

251414

Hom.:

AF XY:

0.0214

AC XY:

2906

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0657

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0270

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.0224

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0188

AC:

27415

AN:

1461752

Hom.:

371

Cov.:

AF XY:

0.0196

AC XY:

14244

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.0223

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.00182

Gnomad4 NFE exome

AF:

0.0185

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.0158

AC:

2409

AN:

152258

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.0201

Gnomad4 OTH

AF:

0.0351

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

DANN

Benign

0.70

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

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