NM_004425.4:c.71-269C>T

Variant names:

• chr1-150509262-C-T
• rs11205386
• NM_004425.4:c.71-269C>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.71-269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 553,420 control chromosomes in the GnomAD database, including 3,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (887 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2190 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.344
• Publications: 3 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 1-150509262-C-T is Benign according to our data. Variant chr1-150509262-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 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.71-269C>T		intron	N/A	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.71-269C>T		intron	N/A	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.71-269C>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.71-269C>T		intron	N/A	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.71-269C>T		intron	N/A	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.71-269C>T		intron	N/A	ENSP00000525906.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15538 AN: 152000 Hom.: 886 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0803

GnomAD4 exome AF: 0.0952 AC: 38197 AN: 401302 Hom.: 2190 Cov.: 0 AF XY: 0.0904 AC XY: 19203 AN XY: 212406

African (AFR) AF: 0.0986 AC: 1122 AN: 11374

American (AMR) AF: 0.0601 AC: 1061 AN: 17650

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 1214 AN: 12178

East Asian (EAS) AF: 0.00 AC: 0 AN: 26516

South Asian (SAS) AF: 0.0318 AC: 1434 AN: 45058

European-Finnish (FIN) AF: 0.135 AC: 3503 AN: 25944

Middle Eastern (MID) AF: 0.0830 AC: 144 AN: 1734

European-Non Finnish (NFE) AF: 0.115 AC: 27469 AN: 237914

Other (OTH) AF: 0.0981 AC: 2250 AN: 22934

GnomAD4 genome AF: 0.102 AC: 15546 AN: 152118 Hom.: 887 Cov.: 32 AF XY: 0.100 AC XY: 7473 AN XY: 74360

African (AFR) AF: 0.0947 AC: 3930 AN: 41492

American (AMR) AF: 0.0723 AC: 1105 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10580

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8139 AN: 67974

Other (OTH) AF: 0.0795 AC: 168 AN: 2114

Alfa AF: 0.108 Hom.: 366

Bravo AF: 0.0959

Asia WGS AF: 0.0230 AC: 81 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	1.5
DANN	Benign	0.33
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11205386; hg19: chr1-150481738;