rs56229218
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_002458.3(MUC5B):c.15972T>C(p.Leu5324=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,537,202 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.025 ( 64 hom., cov: 31)
Exomes 𝑓: 0.011 ( 349 hom. )
Consequence
MUC5B
NM_002458.3 synonymous
NM_002458.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.64
Genes affected
MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
Variant 11-1255464-T-C is Benign according to our data. Variant chr11-1255464-T-C is described in ClinVar as [Benign]. Clinvar id is 178795.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.64 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3774/151982) while in subpopulation NFE AF= 0.0325 (2206/67880). AF 95% confidence interval is 0.0314. There are 64 homozygotes in gnomad4. There are 1873 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3775 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.15972T>C | p.Leu5324= | synonymous_variant | 37/49 | ENST00000529681.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.15972T>C | p.Leu5324= | synonymous_variant | 37/49 | 5 | NM_002458.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0249 AC: 3775AN: 151864Hom.: 64 Cov.: 31
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GnomAD3 exomes AF: 0.0124 AC: 2577AN: 207460Hom.: 59 AF XY: 0.0118 AC XY: 1334AN XY: 113070
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GnomAD4 exome AF: 0.0106 AC: 14721AN: 1385220Hom.: 349 Cov.: 35 AF XY: 0.0109 AC XY: 7504AN XY: 688922
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GnomAD4 genome ? AF: 0.0248 AC: 3774AN: 151982Hom.: 64 Cov.: 31 AF XY: 0.0252 AC XY: 1873AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Leu5324Leu in exon 37 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 3.1% (256/8274) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56229218). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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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