chr1-150509929-C-T

Variant names:

• chr1-150509929-C-T
• rs115614690
• NM_004425.4:c.231C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004425.4(ECM1):​c.231C>T​(p.Pro77Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,614,084 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (10 hom.)
• Consequence: ECM1 NM_004425.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.123
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-150509929-C-T is Benign according to our data. Variant chr1-150509929-C-T is described in ClinVar as Benign. ClinVar VariationId is 772686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.123 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00732 (1115/152224) while in subpopulation AFR AF = 0.0259 (1076/41532). AF 95% confidence interval is 0.0246. There are 17 homozygotes in GnomAd4. There are 506 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.231C>T	p.Pro77Pro	synonymous	Exon 4 of 10	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.312C>T	p.Pro104Pro	synonymous	Exon 4 of 10	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.231C>T	p.Pro77Pro	synonymous	Exon 4 of 9	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.231C>T	p.Pro77Pro	synonymous	Exon 4 of 10	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.231C>T	p.Pro77Pro	synonymous	Exon 4 of 9	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.318C>T	p.Pro106Pro	synonymous	Exon 4 of 10	ENSP00000525906.1

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1112 AN: 152106 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00191 AC: 481 AN: 251400 AF XY: 0.00123

Gnomad AFR exome AF: 0.0276

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000731 AC: 1068 AN: 1461860 Hom.: 10 Cov.: 36 AF XY: 0.000615 AC XY: 447 AN XY: 727230

African (AFR) AF: 0.0272 AC: 909 AN: 33478

American (AMR) AF: 0.000939 AC: 42 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111986

Other (OTH) AF: 0.00149 AC: 90 AN: 60394

GnomAD4 genome AF: 0.00732 AC: 1115 AN: 152224 Hom.: 17 Cov.: 32 AF XY: 0.00680 AC XY: 506 AN XY: 74432

African (AFR) AF: 0.0259 AC: 1076 AN: 41532

American (AMR) AF: 0.00170 AC: 26 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00444 Hom.: 6

Bravo AF: 0.00855

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	-0.86
CADD	Benign	5.5
DANN	Benign	0.48
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs115614690; hg19: chr1-150482405;