1-150509420-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.475

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.71-111C>T		intron_variant		ENST00000369047.9
ECM1	NM_001202858.2	c.71-111C>T		intron_variant
ECM1	NM_022664.3	c.71-111C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4982 AN: 152076 Hom.: 108 Cov.: 32

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.: 14 AF XY: 0.0221 AC XY: 11686 AN XY: 528302

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.: 32 AF XY: 0.0315 AC XY: 2344 AN XY: 74404

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.: 16

Bravo AF: 0.0356

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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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

Other links and lift over

dbSNP: rs116804526; hg19: chr1-150481896;