1-150509779-A-G

Position:

• chr1-150509779-A-G

Variant summary

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

The NM_004425.4(ECM1):​c.223+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,611,474 control chromosomes in the GnomAD database, including 13,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (903 hom., cov: 31)
  • Exomes 𝑓: 0.12 (12601 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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=-0.91).
• BP6: Variant 1-150509779-A-G is Benign according to our data. Variant chr1-150509779-A-G is described in ClinVar as [Benign]. Clinvar id is 1238731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECM1	NM_004425.4	c.223+17A>G		intron_variant		ENST00000369047.9
ECM1	NM_001202858.2	c.217+23A>G		intron_variant
ECM1	NM_022664.3	c.223+17A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECM1	ENST00000369047.9	c.223+17A>G		intron_variant		1	NM_004425.4	P1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14519 AN: 150594 Hom.: 903 Cov.: 31

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000791

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.0858

GnomAD3 exomes AF: 0.0968 AC: 24311 AN: 251252 Hom.: 1582 AF XY: 0.0969 AC XY: 13159 AN XY: 135800

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.0507

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0356

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.124 AC: 181172 AN: 1460768 Hom.: 12601 Cov.: 37 AF XY: 0.122 AC XY: 88545 AN XY: 726752

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0963 AC: 14515 AN: 150706 Hom.: 903 Cov.: 31 AF XY: 0.0948 AC XY: 6982 AN XY: 73636

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.000793

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.124 Hom.: 357

Bravo AF: 0.0850

Asia WGS AF: 0.0210 AC: 76 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	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.011
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs41264469; hg19: chr1-150482255;