rs201746407
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_002458.3(MUC5B):c.16273G>A(p.Gly5425Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,608,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 1 hom. )
Consequence
MUC5B
NM_002458.3 missense
NM_002458.3 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 1.04
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 Likely_benign. Variant got -6 ACMG points.
BP6
Variant 11-1257533-G-A is Benign according to our data. Variant chr11-1257533-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164007.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 144 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.16273G>A | p.Gly5425Arg | missense_variant | 41/49 | ENST00000529681.5 | NP_002449.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.16273G>A | p.Gly5425Arg | missense_variant | 41/49 | 5 | NM_002458.3 | ENSP00000436812 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000946 AC: 144AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000316 AC: 77AN: 243714Hom.: 0 AF XY: 0.000255 AC XY: 34AN XY: 133186
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GnomAD4 exome AF: 0.0000989 AC: 144AN: 1455870Hom.: 1 Cov.: 32 AF XY: 0.0000897 AC XY: 65AN XY: 724350
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GnomAD4 genome AF: 0.000946 AC: 144AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2016 | p.Gly5425Arg in exon 41 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 0.4% (34/9248) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP; rs201746407). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Vest4
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at