chr11-1250278-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):​c.13398G>A​(p.Thr4466Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,611,090 control chromosomes in the GnomAD database, including 80,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7153 hom., cov: 30)
Exomes 𝑓: 0.31 ( 73293 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.38

Publications

7 publications found
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]
MUC5B Gene-Disease associations (from GenCC):
  • interstitial lung disease
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 11-1250278-G-A is Benign according to our data. Variant chr11-1250278-G-A is described in ClinVar as [Benign]. Clinvar id is 403176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.38 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC5BNM_002458.3 linkc.13398G>A p.Thr4466Thr synonymous_variant Exon 31 of 49 ENST00000529681.5 NP_002449.2 Q9HC84

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkc.13398G>A p.Thr4466Thr synonymous_variant Exon 31 of 49 5 NM_002458.3 ENSP00000436812.1 Q9HC84

Frequencies

GnomAD3 genomes
AF:
0.295
AC:
44186
AN:
149938
Hom.:
7138
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.218
Gnomad AMI
AF:
0.362
Gnomad AMR
AF:
0.328
Gnomad ASJ
AF:
0.299
Gnomad EAS
AF:
0.597
Gnomad SAS
AF:
0.292
Gnomad FIN
AF:
0.286
Gnomad MID
AF:
0.261
Gnomad NFE
AF:
0.311
Gnomad OTH
AF:
0.313
GnomAD2 exomes
AF:
0.320
AC:
78854
AN:
246290
AF XY:
0.319
show subpopulations
Gnomad AFR exome
AF:
0.201
Gnomad AMR exome
AF:
0.305
Gnomad ASJ exome
AF:
0.295
Gnomad EAS exome
AF:
0.609
Gnomad FIN exome
AF:
0.282
Gnomad NFE exome
AF:
0.315
Gnomad OTH exome
AF:
0.309
GnomAD4 exome
AF:
0.312
AC:
455742
AN:
1461032
Hom.:
73293
Cov.:
120
AF XY:
0.310
AC XY:
225537
AN XY:
726768
show subpopulations
African (AFR)
AF:
0.210
AC:
7028
AN:
33458
American (AMR)
AF:
0.303
AC:
13569
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
0.290
AC:
7579
AN:
26130
East Asian (EAS)
AF:
0.594
AC:
23579
AN:
39694
South Asian (SAS)
AF:
0.281
AC:
24200
AN:
86238
European-Finnish (FIN)
AF:
0.282
AC:
14943
AN:
53046
Middle Eastern (MID)
AF:
0.287
AC:
1643
AN:
5732
European-Non Finnish (NFE)
AF:
0.310
AC:
344275
AN:
1111676
Other (OTH)
AF:
0.314
AC:
18926
AN:
60348
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
26356
52712
79067
105423
131779
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
11340
22680
34020
45360
56700
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.295
AC:
44221
AN:
150058
Hom.:
7153
Cov.:
30
AF XY:
0.296
AC XY:
21642
AN XY:
73200
show subpopulations
African (AFR)
AF:
0.218
AC:
8908
AN:
40920
American (AMR)
AF:
0.329
AC:
4985
AN:
15158
Ashkenazi Jewish (ASJ)
AF:
0.299
AC:
1030
AN:
3442
East Asian (EAS)
AF:
0.597
AC:
3038
AN:
5088
South Asian (SAS)
AF:
0.292
AC:
1386
AN:
4748
European-Finnish (FIN)
AF:
0.286
AC:
2933
AN:
10266
Middle Eastern (MID)
AF:
0.259
AC:
76
AN:
294
European-Non Finnish (NFE)
AF:
0.311
AC:
20868
AN:
67148
Other (OTH)
AF:
0.320
AC:
668
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1490
2979
4469
5958
7448
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
430
860
1290
1720
2150
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.293
Hom.:
1170
Bravo
AF:
0.294
EpiCase
AF:
0.309
EpiControl
AF:
0.313

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Mar 28, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.3
DANN
Benign
0.76
PhyloP100
-3.4
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12418291; hg19: chr11-1271508; COSMIC: COSV71593934; COSMIC: COSV71593934; API