11-1227154-G-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002458.3(MUC5B):c.576+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,606,824 control chromosomes in the GnomAD database, including 894 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: 35)
Exomes 𝑓: 0.030 ( 836 hom. )
Consequence
MUC5B
NM_002458.3 intron
NM_002458.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0320
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 11-1227154-G-T is Benign according to our data. Variant chr11-1227154-G-T is described in ClinVar as [Benign]. Clinvar id is 163994.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1227154-G-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.023 (3501/152350) while in subpopulation NFE AF= 0.033 (2246/68018). AF 95% confidence interval is 0.0319. There are 58 homozygotes in gnomad4. There are 1747 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3501 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUC5B | NM_002458.3 | c.576+9G>T | intron_variant | ENST00000529681.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUC5B | ENST00000529681.5 | c.576+9G>T | intron_variant | 5 | NM_002458.3 | P1 | |||
MUC5B | ENST00000525715.5 | n.634+9G>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0230 AC: 3501AN: 152232Hom.: 58 Cov.: 35
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GnomAD3 exomes AF: 0.0262 AC: 6372AN: 243238Hom.: 131 AF XY: 0.0260 AC XY: 3455AN XY: 132812
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GnomAD4 exome AF: 0.0301 AC: 43732AN: 1454474Hom.: 836 Cov.: 33 AF XY: 0.0294 AC XY: 21256AN XY: 722624
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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 | 576+9G>T in intron 5 of MUC5B: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 3.2% (268/8278) of European American chromosomes f rom a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS; dbSNP rs56394097). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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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