1-150511475-C-G

Variant names:

• chr1-150511475-C-G
• rs746217361
• NM_004425.4:c.727C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004425.4(ECM1):​c.727C>G​(p.Arg243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECM1 NM_004425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet

ENSG00000307101 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3290745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM1	NM_004425.4	c.727C>G	p.Arg243Gly	missense_variant	Exon 7 of 10	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.808C>G	p.Arg270Gly	missense_variant	Exon 7 of 10		NP_001189787.1
ECM1	NM_022664.3	c.708+277C>G		intron_variant	Intron 6 of 8		NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9	c.727C>G	p.Arg243Gly	missense_variant	Exon 7 of 10	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	.;L
PhyloP100		0.31
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.34
Sift	Benign	0.044	D;T
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.91	P;P
Vest4		0.26
MutPred		0.54		.;Gain of sheet (P = 0.0477);
MVP		0.84
MPC		0.37
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.17
gMVP		0.53
Mutation Taster		=91/9	polymorphism

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: rs746217361; hg19: chr1-150483951;