1-150509262-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.71-269C>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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.344

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 1-150509262-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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.71-269C>T		intron_variant		ENST00000369047.9
ECM1	NM_001202858.2	c.71-269C>T		intron_variant
ECM1	NM_022664.3	c.71-269C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15538 AN: 152000 Hom.: 886 Cov.: 32

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.: 0 AF XY: 0.0904 AC XY: 19203 AN XY: 212406

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.: 32 AF XY: 0.100 AC XY: 7473 AN XY: 74360

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: 81 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	1.5
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

Other links and lift over

dbSNP: rs11205386; hg19: chr1-150481738;