rs185838223

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.12537G>C(p.Gln4179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,611,248 control chromosomes in the GnomAD database, including 3,306 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q4179R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.062 ( 348 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2958 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.21

Publications

6 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 links:

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

MUC5B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002925545).

BP6

Variant 11-1249417-G-C is Benign according to our data. Variant chr11-1249417-G-C is described in ClinVar as [Benign]. Clinvar id is 403172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.12537G>C	p.Gln4179His	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+204C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.12537G>C	p.Gln4179His	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+204C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9485

AN:

152076

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0505

Gnomad FIN

AF:

0.0950

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.0536

GnomAD2 exomes

AF:

0.0653

AC:

15984

AN:

244920

AF XY:

0.0605

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0408

Gnomad EAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.0849

Gnomad NFE exome

AF:

0.0522

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0564

AC:

82339

AN:

1459054

Hom.:

2958

Cov.:

118

AF XY:

0.0558

AC XY:

40536

AN XY:

725810

show subpopulations

African (AFR)

AF:

0.0619

AC:

2066

AN:

33396

American (AMR)

AF:

0.146

AC:

6525

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0376

AC:

982

AN:

26130

East Asian (EAS)

AF:

0.00123

AC:

AN:

39698

South Asian (SAS)

AF:

0.0512

AC:

4415

AN:

86164

European-Finnish (FIN)

AF:

0.0825

AC:

4380

AN:

53098

Middle Eastern (MID)

AF:

0.0442

AC:

183

AN:

4144

European-Non Finnish (NFE)

AF:

0.0545

AC:

60599

AN:

1111570

Other (OTH)

AF:

0.0522

AC:

3140

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7048

14097

21145

28194

35242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0623

AC:

9489

AN:

152194

Hom.:

348

Cov.:

AF XY:

0.0653

AC XY:

4861

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0634

AC:

2629

AN:

41494

American (AMR)

AF:

0.109

AC:

1674

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.0503

AC:

243

AN:

4830

European-Finnish (FIN)

AF:

0.0950

AC:

1008

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0531

AC:

3609

AN:

68002

Other (OTH)

AF:

0.0531

AC:

112

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

449

897

1346

1794

2243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0556

Hom.:

Bravo

AF:

0.0645

ESP6500AA

AF:

0.0626

AC:

237

ESP6500EA

AF:

0.0528

AC:

432

ExAC

AF:

0.0598

AC:

7160

EpiCase

AF:

0.0497

EpiControl

AF:

0.0465

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 -

Interstitial lung disease 2

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.015

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.039

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

PhyloP100

-1.2

PrimateAI

Benign

0.41

PROVEAN

Benign

0.17

REVEL

Benign

0.076

Sift

Benign

0.51

Vest4

0.068

ClinPred

0.0027

GERP RS

-7.3

Varity_R

0.067

gMVP

0.72

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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rs185838223

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over