rs75772057

Variant names:

• chr1-150509506-C-T
• rs75772057
• NM_004425.4:c.71-25C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004425.4(ECM1):​c.71-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,614,010 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (32 hom., cov: 32)
  • Exomes 𝑓: 0.019 (371 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0850
• Publications: 2 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ENSG00000307101 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-150509506-C-T is Benign according to our data. Variant chr1-150509506-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1206950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0158 (2409/152258) while in subpopulation AMR AF = 0.032 (489/15284). AF 95% confidence interval is 0.0297. There are 32 homozygotes in GnomAd4. There are 1135 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

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.71-25C>T		intron	N/A	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.71-25C>T		intron	N/A	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.71-25C>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.71-25C>T		intron	N/A	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.71-25C>T		intron	N/A	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.71-25C>T		intron	N/A	ENSP00000525906.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2412 AN: 152140 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0200 AC: 5025 AN: 251414 AF XY: 0.0214

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.0216

Gnomad ASJ exome AF: 0.0657

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.0224

Gnomad OTH exome AF: 0.0282

GnomAD4 exome AF: 0.0188 AC: 27415 AN: 1461752 Hom.: 371 Cov.: 31 AF XY: 0.0196 AC XY: 14244 AN XY: 727180

African (AFR) AF: 0.00299 AC: 100 AN: 33478

American (AMR) AF: 0.0223 AC: 996 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1614 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0278 AC: 2398 AN: 86250

European-Finnish (FIN) AF: 0.00182 AC: 97 AN: 53414

Middle Eastern (MID) AF: 0.0479 AC: 276 AN: 5766

European-Non Finnish (NFE) AF: 0.0185 AC: 20607 AN: 1111896

Other (OTH) AF: 0.0219 AC: 1323 AN: 60392

GnomAD4 genome AF: 0.0158 AC: 2409 AN: 152258 Hom.: 32 Cov.: 32 AF XY: 0.0152 AC XY: 1135 AN XY: 74448

African (AFR) AF: 0.00361 AC: 150 AN: 41542

American (AMR) AF: 0.0320 AC: 489 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4822

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1366 AN: 68022

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0254 Hom.: 18

Bravo AF: 0.0177

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.84
CADD	Benign	6.0
DANN	Benign	0.70
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75772057; hg19: chr1-150481982;