chr1-150509668-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_004425.4(ECM1):c.129C>T(p.Tyr43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,613,748 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 1 hom. )
Consequence
ECM1
NM_004425.4 synonymous
NM_004425.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.174
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 1-150509668-C-T is Benign according to our data. Variant chr1-150509668-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058755.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.174 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000753 (110/1461682) while in subpopulation EAS AF= 0.00108 (43/39700). AF 95% confidence interval is 0.000826. There are 1 homozygotes in gnomad4_exome. There are 54 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECM1 | NM_004425.4 | c.129C>T | p.Tyr43= | synonymous_variant | 3/10 | ENST00000369047.9 | |
ECM1 | NM_001202858.2 | c.129C>T | p.Tyr43= | synonymous_variant | 3/10 | ||
ECM1 | NM_022664.3 | c.129C>T | p.Tyr43= | synonymous_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECM1 | ENST00000369047.9 | c.129C>T | p.Tyr43= | synonymous_variant | 3/10 | 1 | NM_004425.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000856 AC: 13AN: 151948Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251430Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135884
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GnomAD4 exome AF: 0.0000753 AC: 110AN: 1461682Hom.: 1 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727162
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GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74356
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ECM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 03, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at