rs550578181

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002458.3(MUC5B):​c.5620G>A​(p.Val1874Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,613,704 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1874L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.600

Publications

2 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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007662475).
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC5BNM_002458.3 linkc.5620G>A p.Val1874Met missense_variant Exon 31 of 49 ENST00000529681.5 NP_002449.2 Q9HC84
MUC5B-AS1NR_157183.1 linkn.195C>T non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkc.5620G>A p.Val1874Met missense_variant Exon 31 of 49 5 NM_002458.3 ENSP00000436812.1 Q9HC84
MUC5B-AS1ENST00000532061.2 linkn.195C>T non_coding_transcript_exon_variant Exon 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
151980
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000915
AC:
228
AN:
249258
AF XY:
0.00121
show subpopulations
Gnomad AFR exome
AF:
0.0000642
Gnomad AMR exome
AF:
0.000522
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000392
AC:
573
AN:
1461606
Hom.:
5
Cov.:
80
AF XY:
0.000556
AC XY:
404
AN XY:
727090
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.000380
AC:
17
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00603
AC:
520
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53374
Middle Eastern (MID)
AF:
0.000347
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000126
AC:
14
AN:
1111816
Other (OTH)
AF:
0.000315
AC:
19
AN:
60366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
54
109
163
218
272
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.000283
AC:
43
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.000471
AC XY:
35
AN XY:
74366
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41434
American (AMR)
AF:
0.00150
AC:
23
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00414
AC:
20
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67986
Other (OTH)
AF:
0.00
AC:
0
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.518
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000128
Hom.:
0
Bravo
AF:
0.000189
ExAC
AF:
0.000972
AC:
118
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
15
DANN
Benign
0.88
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.0036
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.0077
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.8
M
PhyloP100
-0.60
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.096
Sift
Uncertain
0.021
D
Vest4
0.086
MVP
0.082
ClinPred
0.089
T
GERP RS
-3.9
Varity_R
0.10
gMVP
0.81
Mutation Taster
=100/0
polymorphism

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: rs550578181; hg19: chr11-1263730; COSMIC: COSV107533041; COSMIC: COSV107533041; API