rs55770822

Variant names:

• chr1-150511841-C-T
• rs55770822
• NM_004425.4:c.1083+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-150511841-C-T
• chr1-150511841-C-A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 Benign/Likely_benign. ClinVar VariationId is 445438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 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.1083+10C>T		intron	N/A	NP_004416.2	A0A140VJI7
	ECM1	NM_001202858.2		c.1164+10C>T		intron	N/A	NP_001189787.1	Q16610-4
	ECM1	NM_022664.3		c.709-511C>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.1083+10C>T		intron	N/A	ENSP00000358043.4	Q16610-1
	ECM1	ENST00000346569.6	TSL:1	c.709-511C>T		intron	N/A	ENSP00000271630.6	Q16610-2
	ECM1	ENST00000855847.1		c.1170+10C>T		intron	N/A	ENSP00000525906.1

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

GnomAD2 exomes AF: 0.00374 AC: 865 AN: 231572 AF XY: 0.00368

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 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

African (AFR) AF: 0.000455 AC: 15 AN: 32936

American (AMR) AF: 0.000490 AC: 21 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.000770 AC: 19 AN: 24666

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39464

South Asian (SAS) AF: 0.000240 AC: 20 AN: 83370

European-Finnish (FIN) AF: 0.0193 AC: 1009 AN: 52278

Middle Eastern (MID) AF: 0.000556 AC: 3 AN: 5396

European-Non Finnish (NFE) AF: 0.00356 AC: 3919 AN: 1099768

Other (OTH) AF: 0.00222 AC: 132 AN: 59338

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

African (AFR) AF: 0.000531 AC: 22 AN: 41468

American (AMR) AF: 0.000655 AC: 10 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.0186 AC: 196 AN: 10562

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

European-Non Finnish (NFE) AF: 0.00355 AC: 241 AN: 67966

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00283 Hom.: 0

Bravo AF: 0.00189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Lipid proteinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.74
PhyloP100		-0.062
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55770822; hg19: chr1-150484317;