1-150509420-C-T

Variant names:

• chr1-150509420-C-T
• rs116804526
• NM_004425.4:c.71-111C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004425.4(ECM1):​c.71-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,178,012 control chromosomes in the GnomAD database, including 439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (107 hom., cov: 32)
  • Exomes 𝑓: 0.023 (332 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.475
• Publications: 0 publications found

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]

ECM1 Gene-Disease associations (from GenCC):

• lipoid proteinosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P

ENSG00000307101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-150509420-C-T is Benign according to our data. Variant chr1-150509420-C-T is described in ClinVar as Benign. ClinVar VariationId is 1230177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECM1	NM_004425.4	MANE Select	c.71-111C>T		intron	N/A	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.71-111C>T		intron	N/A	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.71-111C>T		intron	N/A	NP_073155.2	Q16610-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECM1	ENST00000369047.9	TSL:1 MANE Select	c.71-111C>T		intron	N/A	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.71-111C>T		intron	N/A	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.71-111C>T		intron	N/A	ENSP00000525906.1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4982 AN: 152076 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0227 AC: 23278 AN: 1025818 Hom.: 332 Cov.: 14 AF XY: 0.0221 AC XY: 11686 AN XY: 528302

African (AFR) AF: 0.0596 AC: 1481 AN: 24858

American (AMR) AF: 0.0191 AC: 786 AN: 41112

Ashkenazi Jewish (ASJ) AF: 0.0500 AC: 1161 AN: 23204

East Asian (EAS) AF: 0.0000810 AC: 3 AN: 37016

South Asian (SAS) AF: 0.00839 AC: 634 AN: 75568

European-Finnish (FIN) AF: 0.00820 AC: 409 AN: 49880

Middle Eastern (MID) AF: 0.0446 AC: 168 AN: 3770

European-Non Finnish (NFE) AF: 0.0238 AC: 17273 AN: 724430

Other (OTH) AF: 0.0296 AC: 1363 AN: 45980

GnomAD4 genome AF: 0.0327 AC: 4979 AN: 152194 Hom.: 107 Cov.: 32 AF XY: 0.0315 AC XY: 2344 AN XY: 74404

African (AFR) AF: 0.0581 AC: 2412 AN: 41490

American (AMR) AF: 0.0287 AC: 439 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4830

European-Finnish (FIN) AF: 0.00734 AC: 78 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1695 AN: 68004

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0276 Hom.: 114

Bravo AF: 0.0356

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116804526; hg19: chr1-150481896;