11-1249847-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):​c.12967G>T​(p.Val4323Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 148,352 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 53 hom., cov: 31)
Exomes 𝑓: 0.030 ( 859 hom. )
Failed GnomAD Quality Control

Consequence

MUC5B
NM_002458.3 missense

Scores

17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.37
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0028523505).
BP6
Variant 11-1249847-G-T is Benign according to our data. Variant chr11-1249847-G-T is described in ClinVar as [Benign]. Clinvar id is 403173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0235 (3479/148352) while in subpopulation NFE AF= 0.0304 (2040/67158). AF 95% confidence interval is 0.0293. There are 53 homozygotes in gnomad4. There are 1730 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 3479 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUC5BNM_002458.3 linkuse as main transcriptc.12967G>T p.Val4323Phe missense_variant 31/49 ENST00000529681.5 NP_002449.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkuse as main transcriptc.12967G>T p.Val4323Phe missense_variant 31/495 NM_002458.3 ENSP00000436812 P1

Frequencies

GnomAD3 genomes
AF:
0.0235
AC:
3477
AN:
148228
Hom.:
53
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0138
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00702
Gnomad ASJ
AF:
0.0276
Gnomad EAS
AF:
0.00105
Gnomad SAS
AF:
0.00688
Gnomad FIN
AF:
0.0593
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0303
Gnomad OTH
AF:
0.0206
GnomAD3 exomes
AF:
0.0176
AC:
4297
AN:
244506
Hom.:
127
AF XY:
0.0173
AC XY:
2290
AN XY:
132632
show subpopulations
Gnomad AFR exome
AF:
0.0127
Gnomad AMR exome
AF:
0.00300
Gnomad ASJ exome
AF:
0.0112
Gnomad EAS exome
AF:
0.00122
Gnomad SAS exome
AF:
0.00475
Gnomad FIN exome
AF:
0.0601
Gnomad NFE exome
AF:
0.0216
Gnomad OTH exome
AF:
0.0159
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0298
AC:
43537
AN:
1459006
Hom.:
859
Cov.:
107
AF XY:
0.0291
AC XY:
21115
AN XY:
725744
show subpopulations
Gnomad4 AFR exome
AF:
0.0127
Gnomad4 AMR exome
AF:
0.00529
Gnomad4 ASJ exome
AF:
0.0265
Gnomad4 EAS exome
AF:
0.00218
Gnomad4 SAS exome
AF:
0.00932
Gnomad4 FIN exome
AF:
0.0716
Gnomad4 NFE exome
AF:
0.0323
Gnomad4 OTH exome
AF:
0.0272
GnomAD4 genome
AF:
0.0235
AC:
3479
AN:
148352
Hom.:
53
Cov.:
31
AF XY:
0.0239
AC XY:
1730
AN XY:
72372
show subpopulations
Gnomad4 AFR
AF:
0.0138
Gnomad4 AMR
AF:
0.00702
Gnomad4 ASJ
AF:
0.0276
Gnomad4 EAS
AF:
0.00126
Gnomad4 SAS
AF:
0.00688
Gnomad4 FIN
AF:
0.0593
Gnomad4 NFE
AF:
0.0304
Gnomad4 OTH
AF:
0.0204
Alfa
AF:
0.0179
Hom.:
20
ExAC
AF:
0.0274
AC:
3325

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.061
DANN
Benign
0.52
DEOGEN2
Benign
0.022
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.0013
N
LIST_S2
Benign
0.35
T
MetaRNN
Benign
0.0029
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.014
Sift
Benign
0.034
D
Vest4
0.021
ClinPred
0.0030
T
GERP RS
-1.5
Varity_R
0.058
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201326462; hg19: chr11-1271077; COSMIC: COSV71591798; COSMIC: COSV71591798; API