rs606231159
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001042545.2(LTBP4):c.3464delA(p.Gln1155ArgfsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Q1155Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
LTBP4
NM_001042545.2 frameshift
NM_001042545.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.46
Publications
0 publications found
Genes affected
LTBP4 (HGNC:6717): (latent transforming growth factor beta binding protein 4) The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
LTBP4 Gene-Disease associations (from GenCC):
- cutis laxa with severe pulmonary, gastrointestinal and urinary anomaliesInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-40622646-CA-C is Pathogenic according to our data. Variant chr19-40622646-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 5395.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LTBP4 | NM_001042545.2 | c.3464delA | p.Gln1155ArgfsTer27 | frameshift_variant | Exon 23 of 30 | ENST00000396819.8 | NP_001036010.1 | |
| LTBP4 | NM_001042544.1 | c.3665delA | p.Gln1222ArgfsTer27 | frameshift_variant | Exon 26 of 33 | NP_001036009.1 | ||
| LTBP4 | NM_003573.2 | c.3554delA | p.Gln1185ArgfsTer27 | frameshift_variant | Exon 26 of 33 | NP_003564.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453318Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 721794 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1453318
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
721794
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33332
American (AMR)
AF:
AC:
0
AN:
44442
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25954
East Asian (EAS)
AF:
AC:
0
AN:
39526
South Asian (SAS)
AF:
AC:
0
AN:
85942
European-Finnish (FIN)
AF:
AC:
0
AN:
51398
Middle Eastern (MID)
AF:
AC:
0
AN:
5440
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1107354
Other (OTH)
AF:
AC:
0
AN:
59930
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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8
10
<30
30-35
35-40
40-45
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50-55
55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies Pathogenic:1
Nov 01, 2009
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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