Variant chr1-150509262-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.71-269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 553,420 control chromosomes in the GnomAD database, including 3,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 887 hom., cov: 32)

Exomes 𝑓: 0.095 ( 2190 hom. )

Consequence

ECM1
NM_004425.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.344

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 (BayesDel_noAF=-0.89).

BP6

Variant 1-150509262-C-T is Benign according to our data. Variant chr1-150509262-C-T is described in ClinVar as [Benign]. Clinvar id is 1271709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ECM1	NM_004425.4 linkuse as main transcript	c.71-269C>T	intron_variant	ENST00000369047.9
ECM1	NM_001202858.2 linkuse as main transcript	c.71-269C>T	intron_variant
ECM1	NM_022664.3 linkuse as main transcript	c.71-269C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9 linkuse as main transcript	c.71-269C>T		intron_variant		1	NM_004425.4	P1	Q16610-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15538

AN:

152000

Hom.:

886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0947

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0724

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0803

GnomAD4 exome

AF:

0.0952

AC:

38197

AN:

401302

Hom.:

2190

Cov.:

AF XY:

0.0904

AC XY:

19203

AN XY:

212406

show subpopulations

Gnomad4 AFR exome

AF:

0.0986

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0997

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0318

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.0981

GnomAD4 genome

AF:

0.102

AC:

15546

AN:

152118

Hom.:

887

Cov.:

AF XY:

0.100

AC XY:

7473

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0947

Gnomad4 AMR

AF:

0.0723

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.107

Hom.:

306

Bravo

AF:

0.0959

Asia WGS

AF:

0.0230

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

1.5

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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