NM_004425.4:c.-97G>A

Variant names:

• chr1-150508113-G-A
• rs116220997
• NM_004425.4:c.-97G>A

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.-97G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,161,188 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (163 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (134 hom.)
• Consequence: ECM1 NM_004425.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.422
• 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: 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=-0.84).
• BP6: Variant 1-150508113-G-A is Benign according to our data. Variant chr1-150508113-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 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.-97G>A		5_prime_UTR	Exon 1 of 10	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.-97G>A		5_prime_UTR	Exon 1 of 10	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.-97G>A		5_prime_UTR	Exon 1 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.-97G>A		5_prime_UTR	Exon 1 of 10	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.-97G>A		5_prime_UTR	Exon 1 of 9	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.-97G>A		5_prime_UTR	Exon 1 of 10	ENSP00000525906.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3835 AN: 152124 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00331 AC: 3335 AN: 1008946 Hom.: 134 Cov.: 14 AF XY: 0.00281 AC XY: 1463 AN XY: 521236

African (AFR) AF: 0.0916 AC: 2260 AN: 24666

American (AMR) AF: 0.00491 AC: 216 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 9 AN: 23270

East Asian (EAS) AF: 0.0000533 AC: 2 AN: 37550

South Asian (SAS) AF: 0.000364 AC: 28 AN: 76858

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48316

Middle Eastern (MID) AF: 0.0120 AC: 59 AN: 4920

European-Non Finnish (NFE) AF: 0.000624 AC: 439 AN: 703768

Other (OTH) AF: 0.00703 AC: 321 AN: 45636

GnomAD4 genome AF: 0.0252 AC: 3844 AN: 152242 Hom.: 163 Cov.: 32 AF XY: 0.0239 AC XY: 1778 AN XY: 74440

African (AFR) AF: 0.0870 AC: 3612 AN: 41512

American (AMR) AF: 0.00942 AC: 144 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68026

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.00770 Hom.: 8

Bravo AF: 0.0282

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	-0.84
CADD	Benign	9.3
DANN	Benign	0.64
PhyloP100		0.42
PromoterAI		-0.24	Neutral
Mutation Taster		=300/0	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: rs116220997; hg19: chr1-150480589;