rs1051303
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001042545.2(LTBP4):āc.2257A>Gā(p.Thr753Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,610,370 control chromosomes in the GnomAD database, including 151,226 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_001042545.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTBP4 | NM_001042545.2 | c.2257A>G | p.Thr753Ala | missense_variant | 15/30 | ENST00000396819.8 | NP_001036010.1 | |
LTBP4 | NM_001042544.1 | c.2458A>G | p.Thr820Ala | missense_variant | 18/33 | NP_001036009.1 | ||
LTBP4 | NM_003573.2 | c.2347A>G | p.Thr783Ala | missense_variant | 18/33 | NP_003564.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LTBP4 | ENST00000396819.8 | c.2257A>G | p.Thr753Ala | missense_variant | 15/30 | 1 | NM_001042545.2 | ENSP00000380031 | P3 |
Frequencies
GnomAD3 genomes AF: 0.472 AC: 71656AN: 151834Hom.: 17536 Cov.: 32
GnomAD3 exomes AF: 0.440 AC: 107030AN: 243468Hom.: 24222 AF XY: 0.448 AC XY: 59099AN XY: 131998
GnomAD4 exome AF: 0.424 AC: 617917AN: 1458418Hom.: 133682 Cov.: 52 AF XY: 0.430 AC XY: 311594AN XY: 725092
GnomAD4 genome AF: 0.472 AC: 71707AN: 151952Hom.: 17544 Cov.: 32 AF XY: 0.477 AC XY: 35408AN XY: 74296
ClinVar
Submissions by phenotype
Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies Benign:4
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Dec 01, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Thr820Ala in exon 18 of LTBP4: This variant is not expected to have clinical sig nificance because it has been identified in 43.2% (1798/4158) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1051303). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at