rs55784821
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_002458.3(MUC5B):c.16476G>A(p.Gln5492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,594,276 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.023 ( 58 hom., cov: 32)
Exomes 𝑓: 0.030 ( 812 hom. )
Consequence
MUC5B
NM_002458.3 synonymous
NM_002458.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.369
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=-0.81).
BP6
?
Variant 11-1258124-G-A is Benign according to our data. Variant chr11-1258124-G-A is described in ClinVar as [Benign]. Clinvar id is 226735.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1258124-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.369 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3479/152330) while in subpopulation NFE AF= 0.0327 (2227/68014). AF 95% confidence interval is 0.0316. There are 58 homozygotes in gnomad4. There are 1736 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3479 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.16476G>A | p.Gln5492= | synonymous_variant | 42/49 | ENST00000529681.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.16476G>A | p.Gln5492= | synonymous_variant | 42/49 | 5 | NM_002458.3 | P1 | |
MUC5B | ENST00000526859.1 | c.111G>A | p.Gln37= | synonymous_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0229 AC: 3479AN: 152212Hom.: 58 Cov.: 32
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GnomAD3 exomes AF: 0.0253 AC: 5474AN: 216288Hom.: 111 AF XY: 0.0251 AC XY: 2975AN XY: 118616
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GnomAD4 exome AF: 0.0298 AC: 43002AN: 1441946Hom.: 812 Cov.: 34 AF XY: 0.0292 AC XY: 20889AN XY: 715538
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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 | Apr 10, 2015 | p.Gln5492Gln in exon 42 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 7.3% (1647/22468) of European chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs55784821). - |
Computational scores
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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