11-1226228-C-T

Variant names:

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.151C>T(p.Arg51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,554,864 control chromosomes in the GnomAD database, including 9,376 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 (★★).

Frequency

Genomes: 𝑓 0.12 ( 1434 hom., cov: 34)

Exomes 𝑓: 0.091 ( 7942 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.37

Publications

27 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.137358E-4).

BP6

Variant 11-1226228-C-T is Benign according to our data. Variant chr11-1226228-C-T is described in ClinVar as [Benign]. Clinvar id is 163991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 3 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.151C>T	p.Arg51Trp	missense_variant	Exon 3 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.209C>T		non_coding_transcript_exon_variant	Exon 3 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18602

AN:

152128

Hom.:

1434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.114

AC:

18549

AN:

163408

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0747

Gnomad ASJ exome

AF:

0.0510

Gnomad EAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0971

GnomAD4 exome

AF:

0.0913

AC:

128044

AN:

1402618

Hom.:

7942

Cov.:

AF XY:

0.0910

AC XY:

63055

AN XY:

692624

show subpopulations

African (AFR)

AF:

0.176

AC:

5585

AN:

31726

American (AMR)

AF:

0.0789

AC:

2897

AN:

36722

Ashkenazi Jewish (ASJ)

AF:

0.0512

AC:

1293

AN:

25252

East Asian (EAS)

AF:

0.379

AC:

13606

AN:

35920

South Asian (SAS)

AF:

0.128

AC:

10169

AN:

79446

European-Finnish (FIN)

AF:

0.147

AC:

6844

AN:

46526

Middle Eastern (MID)

AF:

0.0640

AC:

366

AN:

5716

European-Non Finnish (NFE)

AF:

0.0751

AC:

81388

AN:

1083098

Other (OTH)

AF:

0.101

AC:

5896

AN:

58212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

6156

12312

18467

24623

30779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.122

AC:

18612

AN:

152246

Hom.:

1434

Cov.:

AF XY:

0.127

AC XY:

9482

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.171

AC:

7085

AN:

41546

American (AMR)

AF:

0.100

AC:

1536

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3472

East Asian (EAS)

AF:

0.370

AC:

1912

AN:

5168

South Asian (SAS)

AF:

0.141

AC:

679

AN:

4824

European-Finnish (FIN)

AF:

0.153

AC:

1621

AN:

10600

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0762

AC:

5182

AN:

68014

Other (OTH)

AF:

0.116

AC:

246

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

839

1677

2516

3354

4193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0896

Hom.:

1912

Bravo

AF:

0.120

TwinsUK

AF:

0.0715

AC:

265

ALSPAC

AF:

0.0776

AC:

299

ESP6500AA

AF:

0.141

AC:

551

ESP6500EA

AF:

0.0699

AC:

569

ExAC

AF:

0.0678

AC:

7345

Asia WGS

AF:

0.270

AC:

940

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg51Trp in exon 3 of MUC5B: This variant is not expected to have clinical signi ficance because it has been identified in 14.1% (551/3908) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs2075853). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.61

MetaRNN

Benign

0.00071

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

PhyloP100

-1.4

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.016

Sift

Benign

0.095

Polyphen

0.0020

Vest4

0.17

ClinPred

0.0055

GERP RS

-3.3

Varity_R

0.035

gMVP

0.81

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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11-1226228-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