1-150509506-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

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=-0.84).
• 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_single_submitter, 1 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 GnomAd at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.71-25C>T		intron_variant		ENST00000369047.9
ECM1	NM_001202858.2	c.71-25C>T		intron_variant
ECM1	NM_022664.3	c.71-25C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2412 AN: 152140 Hom.: 32 Cov.: 32

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.: 93 AF XY: 0.0214 AC XY: 2906 AN XY: 135876

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.: 31 AF XY: 0.0196 AC XY: 14244 AN XY: 727180

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.: 32 Cov.: 32 AF XY: 0.0152 AC XY: 1135 AN XY: 74448

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.: 18

Bravo AF: 0.0177

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs75772057; hg19: chr1-150481982;