rs3829224

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.15721G>A(p.Ala5241Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,592,076 control chromosomes in the GnomAD database, including 2,941 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 467 hom., cov: 33)

Exomes 𝑓: 0.020 ( 2474 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.58

Publications

12 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=0.0034210384).

BP6

Variant 11-1255097-G-A is Benign according to our data. Variant chr11-1255097-G-A is described in ClinVar as Benign. ClinVar VariationId is 226734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.15721G>A	p.Ala5241Thr	missense_variant	Exon 36 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.15721G>A	p.Ala5241Thr	missense_variant	Exon 36 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6760

AN:

152134

Hom.:

468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0426

GnomAD2 exomes

AF:

0.0625

AC:

13152

AN:

210310

AF XY:

0.0586

show subpopulations

Gnomad AFR exome

AF:

0.0872

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.00236

Gnomad EAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.00270

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0203

AC:

29223

AN:

1439824

Hom.:

2474

Cov.:

AF XY:

0.0220

AC XY:

15718

AN XY:

714222

show subpopulations

African (AFR)

AF:

0.0795

AC:

2620

AN:

32964

American (AMR)

AF:

0.135

AC:

5642

AN:

41882

Ashkenazi Jewish (ASJ)

AF:

0.00179

AC:

AN:

25762

East Asian (EAS)

AF:

0.233

AC:

8917

AN:

38286

South Asian (SAS)

AF:

0.109

AC:

8989

AN:

82824

European-Finnish (FIN)

AF:

0.00345

AC:

173

AN:

50206

Middle Eastern (MID)

AF:

0.00783

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000598

AC:

659

AN:

1102546

Other (OTH)

AF:

0.0358

AC:

2132

AN:

59610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1467

2934

4401

5868

7335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.0445

AC:

6777

AN:

152252

Hom.:

467

Cov.:

AF XY:

0.0484

AC XY:

3602

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0820

AC:

3405

AN:

41536

American (AMR)

AF:

0.0755

AC:

1155

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.271

AC:

1402

AN:

5166

South Asian (SAS)

AF:

0.124

AC:

598

AN:

4824

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68010

Other (OTH)

AF:

0.0422

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

296

592

888

1184

1480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0233

Hom.:

549

Bravo

AF:

0.0522

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0770

AC:

322

ESP6500EA

AF:

0.00155

AC:

ExAC

AF:

0.0544

AC:

6487

Asia WGS

AF:

0.162

AC:

565

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Ala5241Thr in exon 36 of MUC5B: This variant is not expected to have clinical si gnificance because it has been identified in 7.7% (322/4182) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs3829224). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.9

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.015

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.32

PhyloP100

-1.6

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.61

REVEL

Benign

0.054

Sift

Benign

0.29

Vest4

0.018

ClinPred

0.00018

GERP RS

-8.4

Varity_R

0.035

gMVP

0.23

Mutation Taster

=100/0

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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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