ENST00000654177.1:n.661G>T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000654177.1(ENSG00000286275):n.661G>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,220 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (★★).
Frequency
Consequence
ENST00000654177.1 splice_region, non_coding_transcript_exon
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 rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENSG00000286275 | ENST00000654177.1 | n.661G>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 2 of 2 |
Frequencies
GnomAD3 genomes AF: 0.0794 AC: 12074AN: 152102Hom.: 595 Cov.: 33
GnomAD4 genome AF: 0.0793 AC: 12074AN: 152220Hom.: 596 Cov.: 33 AF XY: 0.0803 AC XY: 5978AN XY: 74428
ClinVar
Submissions by phenotype
Susceptibility to coronavirus disease (COVID-19) severity and mortality due to low plasma levels of MUC5B Uncertain:1
Differences in plasma levels of MUC5B according to genotypes -
not provided Benign:1
MUC5B: BS1, BS2 -
Antisynthetase syndrome Other:1
Usual Interstitial Pneumonia was observed in the patients -
Interstitial lung disease 2 Other:1
MUC5B c.-3133G>T has been associated with increased risk for idiopathic pulmonary fibrosis. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (16.2%, Genome Aggregation Database (gnomAD); rs35705950) and is present in ClinVar (ID: 30126). Several studies have reported an odds ratios between 3.7-8.3 for developing pulmonary fibrosis in heterozygous individuals (OR=6.3 [95% CI 4.6-8.7] Borie 2013, OR=6.3 [95% CI 3.1-12.7] Hunninghake 2013, OR=8.3 [95% CI 5.8-11.9] Seibold 2013, OR=4.9 [95% CI 3.42-7.03] Stock 2013, OR=5.72 [95% CI 4.7-7.1] Lee 2015, OR=6.2 [95% CI 5.14-7.48] Zhu 2015) and odds ratios between 11.3-21.7 for developing pulmonary fibrosis in homozygous individuals (OR=21.7 [95% CI 104-45.3] Borie 2013, OR=12.98 [95% CI 7.97-21.12] Lee 2015, OR=11.29 [95% CI 5.69-22.40] Zhu 2015). MUC5B c.-3133G>T is a promoter variant that results in increased MUC5B expression (Seibold 2011, Nakano 2016, Kaur 2017). In summary, this variant is an established risk factor for idiopathic pulmonary fibrosis. -
Pulmonary fibrosis, idiopathic, susceptibility to Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at