1-150508113-G-A

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.-97G>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 0.00618 in 1,161,188 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (163 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (134 hom.)
• Consequence: ECM1 NM_004425.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422

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 1-150508113-G-A is Benign according to our data. Variant chr1-150508113-G-A is described in ClinVar as [Benign]. Clinvar id is 1237946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.-97G>A		5_prime_UTR_variant	1/10	ENST00000369047.9
ECM1	NM_001202858.2	c.-97G>A		5_prime_UTR_variant	1/10
ECM1	NM_022664.3	c.-97G>A		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9	c.-97G>A		5_prime_UTR_variant	1/10	1	NM_004425.4	P1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3835 AN: 152124 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00331 AC: 3335 AN: 1008946 Hom.: 134 Cov.: 14 AF XY: 0.00281 AC XY: 1463 AN XY: 521236

Gnomad4 AFR exome AF: 0.0916

Gnomad4 AMR exome AF: 0.00491

Gnomad4 ASJ exome AF: 0.000387

Gnomad4 EAS exome AF: 0.0000533

Gnomad4 SAS exome AF: 0.000364

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.000624

Gnomad4 OTH exome AF: 0.00703

GnomAD4 genome AF: 0.0252 AC: 3844 AN: 152242 Hom.: 163 Cov.: 32 AF XY: 0.0239 AC XY: 1778 AN XY: 74440

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.00346 Hom.: 2

Bravo AF: 0.0282

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 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.3
Dann	Benign	0.64

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: rs116220997; hg19: chr1-150480589;