11-1226739-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002458.3(MUC5B):c.324C>T(p.Arg108Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,612,742 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 37 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.00

Publications

4 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

MUC5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-1226739-C-T is Benign according to our data. Variant chr11-1226739-C-T is described in ClinVar as [Benign]. Clinvar id is 163992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.324C>T	p.Arg108Arg	synonymous_variant	Exon 4 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.324C>T	p.Arg108Arg	synonymous_variant	Exon 4 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.382C>T		non_coding_transcript_exon_variant	Exon 4 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

820

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0134

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00580

AC:

1437

AN:

247590

AF XY:

0.00603

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.00760

Gnomad OTH exome

AF:

0.00699

GnomAD4 exome

AF:

0.00687

AC:

10039

AN:

1460398

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

4962

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33478

American (AMR)

AF:

0.00125

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00390

AC:

336

AN:

86244

European-Finnish (FIN)

AF:

0.0161

AC:

840

AN:

52242

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00760

AC:

8448

AN:

1111796

Other (OTH)

AF:

0.00510

AC:

308

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

688

1376

2063

2751

3439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00538

AC:

819

AN:

152344

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41572

American (AMR)

AF:

0.00124

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00373

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0134

AC:

142

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00822

AC:

559

AN:

68030

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00636

Hom.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00587

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MUC5B: BP4, BP7, BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg108Arg in exon 4 of MUC5B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.8% (70/8502) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs56168747). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.7

(source)

DANN

Benign

0.95

PhyloP100

-6.0

Mutation Taster

=100/0

polymorphism

(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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11-1226739-C-T

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