1-150509668-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1

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 (no stars).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

ECM1
NM_004425.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.174
Variant links:
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 -8 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 no_assertion_criteria_provided, 0 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
ECM1NM_004425.4 linkuse as main transcriptc.129C>T p.Tyr43= synonymous_variant 3/10 ENST00000369047.9
ECM1NM_001202858.2 linkuse as main transcriptc.129C>T p.Tyr43= synonymous_variant 3/10
ECM1NM_022664.3 linkuse as main transcriptc.129C>T p.Tyr43= synonymous_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ECM1ENST00000369047.9 linkuse as main transcriptc.129C>T p.Tyr43= synonymous_variant 3/101 NM_004425.4 P1Q16610-1

Frequencies

GnomAD3 genomes
AF:
0.0000856
AC:
13
AN:
151948
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251430
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000753
AC:
110
AN:
1461682
Hom.:
1
Cov.:
31
AF XY:
0.0000743
AC XY:
54
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00108
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000855
AC:
13
AN:
152066
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000756
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ECM1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 03, 2020This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
11
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201295989; hg19: chr1-150482144; COSMIC: COSV60873421; COSMIC: COSV60873421; API