rs184215485

Variant summary

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

The NM_002458.3(MUC5B):​c.9626G>A​(p.Arg3209Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 150,046 control chromosomes in the GnomAD database, including 68 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 0.025 ( 68 hom., cov: 32)
Exomes 𝑓: 0.026 ( 907 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: -5.15
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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0038914084).
BP6
Variant 11-1246506-G-A is Benign according to our data. Variant chr11-1246506-G-A is described in ClinVar as [Benign]. Clinvar id is 403157.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 = 0.0253 (3799/150046) while in subpopulation NFE AF= 0.033 (2222/67358). AF 95% confidence interval is 0.0318. There are 68 homozygotes in gnomad4. There are 1875 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 3799 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUC5BNM_002458.3 linkc.9626G>A p.Arg3209Lys missense_variant Exon 31 of 49 ENST00000529681.5 NP_002449.2 Q9HC84
MUC5B-AS1NR_157183.1 linkn.56+3115C>T intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUC5BENST00000529681.5 linkc.9626G>A p.Arg3209Lys missense_variant Exon 31 of 49 5 NM_002458.3 ENSP00000436812.1 Q9HC84
MUC5B-AS1ENST00000532061.2 linkn.56+3115C>T intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
AF:
0.0253
AC:
3800
AN:
149924
Hom.:
68
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.00111
Gnomad AMR
AF:
0.00840
Gnomad ASJ
AF:
0.0288
Gnomad EAS
AF:
0.000403
Gnomad SAS
AF:
0.00772
Gnomad FIN
AF:
0.0688
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0330
Gnomad OTH
AF:
0.0223
GnomAD3 exomes
AF:
0.00978
AC:
2370
AN:
242354
Hom.:
112
AF XY:
0.00905
AC XY:
1188
AN XY:
131334
show subpopulations
Gnomad AFR exome
AF:
0.00726
Gnomad AMR exome
AF:
0.00283
Gnomad ASJ exome
AF:
0.00569
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00252
Gnomad FIN exome
AF:
0.0434
Gnomad NFE exome
AF:
0.00996
Gnomad OTH exome
AF:
0.0110
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0257
AC:
37187
AN:
1447650
Hom.:
907
Cov.:
126
AF XY:
0.0251
AC XY:
18060
AN XY:
720182
show subpopulations
Gnomad4 AFR exome
AF:
0.0110
Gnomad4 AMR exome
AF:
0.00480
Gnomad4 ASJ exome
AF:
0.0233
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00772
Gnomad4 FIN exome
AF:
0.0681
Gnomad4 NFE exome
AF:
0.0276
Gnomad4 OTH exome
AF:
0.0234
GnomAD4 genome
AF:
0.0253
AC:
3799
AN:
150046
Hom.:
68
Cov.:
32
AF XY:
0.0256
AC XY:
1875
AN XY:
73240
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.00839
Gnomad4 ASJ
AF:
0.0288
Gnomad4 EAS
AF:
0.000404
Gnomad4 SAS
AF:
0.00773
Gnomad4 FIN
AF:
0.0688
Gnomad4 NFE
AF:
0.0330
Gnomad4 OTH
AF:
0.0221
Alfa
AF:
0.0303
Hom.:
18
Bravo
AF:
0.0204
ExAC
AF:
0.0228
AC:
2770

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

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 -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.0020
DANN
Benign
0.36
DEOGEN2
Benign
0.016
T
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.00030
N
LIST_S2
Benign
0.31
T
MetaRNN
Benign
0.0039
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.4
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.23
N
REVEL
Benign
0.0030
Sift
Benign
0.93
T
Vest4
0.0030
ClinPred
0.0047
T
GERP RS
-1.8
Varity_R
0.040
gMVP
0.17

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: rs184215485; hg19: chr11-1267736; API