rs55770822

Positions:

• chr1-150511841-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004425.4(ECM1):​c.1083+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,592,090 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (17 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0620

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-150511841-C-T is Benign according to our data. Variant chr1-150511841-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150511841-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00316 (480/152004) while in subpopulation NFE AF= 0.00355 (241/67966). AF 95% confidence interval is 0.00318. There are 1 homozygotes in gnomad4. There are 254 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECM1	NM_004425.4	c.1083+10C>T		intron_variant		ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.1164+10C>T		intron_variant			NP_001189787.1
ECM1	NM_022664.3	c.709-511C>T		intron_variant			NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9	c.1083+10C>T		intron_variant		1	NM_004425.4	ENSP00000358043.4
ECM1	ENST00000346569.6	c.709-511C>T		intron_variant		1		ENSP00000271630.6
ECM1	ENST00000369049.8	c.1164+10C>T		intron_variant		2		ENSP00000358045.4
ECM1	ENST00000470432.5	n.2440+10C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 480 AN: 151886 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00355

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00374 AC: 865 AN: 231572 Hom.: 4 AF XY: 0.00368 AC XY: 460 AN XY: 125162

Gnomad AFR exome AF: 0.000569

Gnomad AMR exome AF: 0.000679

Gnomad ASJ exome AF: 0.000742

Gnomad EAS exome AF: 0.000165

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.00363

Gnomad OTH exome AF: 0.00323

GnomAD4 exome AF: 0.00357 AC: 5139 AN: 1440086 Hom.: 17 Cov.: 34 AF XY: 0.00348 AC XY: 2485 AN XY: 713888

Gnomad4 AFR exome AF: 0.000455

Gnomad4 AMR exome AF: 0.000490

Gnomad4 ASJ exome AF: 0.000770

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000240

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.00356

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00316 AC: 480 AN: 152004 Hom.: 1 Cov.: 31 AF XY: 0.00342 AC XY: 254 AN XY: 74278

Gnomad4 AFR AF: 0.000531

Gnomad4 AMR AF: 0.000655

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.00355

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Lipid proteinosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55770822; hg19: chr1-150484317;