1-150509686-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004425.4(ECM1):c.147A>C(p.Pro49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ECM1 NM_004425.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-150509686-A-C is Benign according to our data. Variant chr1-150509686-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 789433.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.147A>C	p.Pro49=	synonymous_variant	3/10	ENST00000369047.9
ECM1	NM_001202858.2	c.147A>C	p.Pro49=	synonymous_variant	3/10
ECM1	NM_022664.3	c.147A>C	p.Pro49=	synonymous_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9	c.147A>C	p.Pro49=	synonymous_variant	3/10	1	NM_004425.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 206 AN: 121494 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00392

Gnomad AMR AF: 0.00127

Gnomad ASJ AF: 0.00102

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000574

Gnomad FIN AF: 0.00152

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00181

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000361 AC: 332 AN: 919218 Hom.: 0 Cov.: 33 AF XY: 0.000355 AC XY: 166 AN XY: 468150

Gnomad4 AFR exome AF: 0.000462

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.000414

Gnomad4 EAS exome AF: 0.000350

Gnomad4 SAS exome AF: 0.000157

Gnomad4 FIN exome AF: 0.000228

Gnomad4 NFE exome AF: 0.000393

Gnomad4 OTH exome AF: 0.000445

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00169 AC: 205 AN: 121600 Hom.: 0 Cov.: 30 AF XY: 0.00202 AC XY: 118 AN XY: 58478

Gnomad4 AFR AF: 0.00194

Gnomad4 AMR AF: 0.00127

Gnomad4 ASJ AF: 0.00102

Gnomad4 EAS AF: 0.00103

Gnomad4 SAS AF: 0.000286

Gnomad4 FIN AF: 0.00152

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.00179

Alfa AF: 0.0305 Hom.: 0

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

Invitae

Jan 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.1
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1364726581; hg19: chr1-150482162;