1-150508095-G-A

Position:

• chr1-150508095-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000369049.8(ECM1):​c.-115G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 949,776 control chromosomes in the GnomAD database, including 3,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (658 hom., cov: 32)
  • Exomes 𝑓: 0.078 (2840 hom.)
• Consequence: ECM1 ENST00000369049.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.69

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-150508095-G-A is Benign according to our data. Variant chr1-150508095-G-A is described in ClinVar as [Benign]. Clinvar id is 1265058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4			upstream_gene_variant		ENST00000369047.9
ECM1	NM_001202858.2			upstream_gene_variant
ECM1	NM_022664.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9			upstream_gene_variant		1	NM_004425.4	P1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12849 AN: 152056 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0725

GnomAD4 exome AF: 0.0777 AC: 61973 AN: 797602 Hom.: 2840 Cov.: 11 AF XY: 0.0752 AC XY: 31798 AN XY: 422668

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0325

Gnomad4 ASJ exome AF: 0.0234

Gnomad4 EAS exome AF: 0.0000823

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.0883

Gnomad4 NFE exome AF: 0.0947

Gnomad4 OTH exome AF: 0.0685

GnomAD4 genome AF: 0.0845 AC: 12862 AN: 152174 Hom.: 658 Cov.: 32 AF XY: 0.0810 AC XY: 6024 AN XY: 74388

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0911

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.0712

Alfa AF: 0.0837 Hom.: 572

Bravo AF: 0.0831

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.83
CADD	Benign	8.4
DANN	Benign	0.56

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: rs12724450; hg19: chr1-150480571;