rs41264469

Variant names:

• chr1-150509779-A-G
• rs41264469
• NM_004425.4:c.223+17A>G

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.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
• 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: 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=-0.91).
• BP6: Variant 1-150509779-A-G is Benign according to our data. Variant chr1-150509779-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.223+17A>G		intron	N/A	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.217+23A>G		intron	N/A	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.223+17A>G		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.223+17A>G		intron	N/A	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.223+17A>G		intron	N/A	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.223+17A>G		intron	N/A	ENSP00000525906.1

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

GnomAD2 exomes AF: 0.0968 AC: 24311 AN: 251252 AF XY: 0.0969

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 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

African (AFR) AF: 0.0199 AC: 667 AN: 33462

American (AMR) AF: 0.0529 AC: 2365 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2976 AN: 26104

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39642

South Asian (SAS) AF: 0.0357 AC: 3081 AN: 86246

European-Finnish (FIN) AF: 0.158 AC: 8432 AN: 53332

Middle Eastern (MID) AF: 0.0760 AC: 438 AN: 5766

European-Non Finnish (NFE) AF: 0.141 AC: 156357 AN: 1111216

Other (OTH) AF: 0.114 AC: 6854 AN: 60304

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

African (AFR) AF: 0.0248 AC: 1013 AN: 40928

American (AMR) AF: 0.0788 AC: 1193 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 393 AN: 3458

East Asian (EAS) AF: 0.000793 AC: 4 AN: 5046

South Asian (SAS) AF: 0.0352 AC: 167 AN: 4746

European-Finnish (FIN) AF: 0.171 AC: 1776 AN: 10396

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9663 AN: 67700

Other (OTH) AF: 0.0849 AC: 177 AN: 2086

Alfa AF: 0.130 Hom.: 644

Bravo AF: 0.0850

Asia WGS AF: 0.0210 AC: 76 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.91
CADD	Benign	0.011
DANN	Benign	0.75
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs41264469; hg19: chr1-150482255;