rs2334757
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002458.3(MUC5B):āc.10821A>Cā(p.Ala3607=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,315,020 control chromosomes in the GnomAD database, including 96,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.33 ( 8667 hom., cov: 26)
Exomes š: 0.24 ( 88289 hom. )
Consequence
MUC5B
NM_002458.3 synonymous
NM_002458.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.66
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 11-1247701-A-C is Benign according to our data. Variant chr11-1247701-A-C is described in ClinVar as [Benign]. Clinvar id is 403165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.66 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.10821A>C | p.Ala3607= | synonymous_variant | 31/49 | ENST00000529681.5 | |
MUC5B-AS1 | NR_157183.1 | n.56+1920T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.10821A>C | p.Ala3607= | synonymous_variant | 31/49 | 5 | NM_002458.3 | P1 | |
MUC5B-AS1 | ENST00000532061.2 | n.56+1920T>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.334 AC: 47027AN: 140838Hom.: 8652 Cov.: 26
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GnomAD3 exomes AF: 0.282 AC: 54820AN: 194570Hom.: 12030 AF XY: 0.279 AC XY: 29514AN XY: 105600
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GnomAD4 exome AF: 0.236 AC: 276554AN: 1174056Hom.: 88289 Cov.: 110 AF XY: 0.238 AC XY: 139730AN XY: 587684
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GnomAD4 genome AF: 0.334 AC: 47088AN: 140964Hom.: 8667 Cov.: 26 AF XY: 0.331 AC XY: 22683AN XY: 68496
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at