rs201530874

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002458.3(MUC5B):c.15560G>A(p.Arg5187His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,612,882 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 20 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.36

Publications

5 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056170225).

BP6

Variant 11-1254776-G-A is Benign according to our data. Variant chr11-1254776-G-A is described in ClinVar as Benign. ClinVar VariationId is 504736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.15560G>A	p.Arg5187His	missense_variant	Exon 35 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.15560G>A	p.Arg5187His	missense_variant	Exon 35 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00291

AC:

720

AN:

247842

AF XY:

0.00346

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00192

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.00196

AC:

2864

AN:

1460556

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

1665

AN XY:

726550

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.00152

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

449

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00850

AC:

733

AN:

86252

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

52404

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00118

AC:

1312

AN:

1111774

Other (OTH)

AF:

0.00335

AC:

202

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

163

327

490

654

817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.00211

AC:

322

AN:

152326

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41582

American (AMR)

AF:

0.00307

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0102

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00201

AC:

137

AN:

68014

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00234

Hom.:

Bravo

AF:

0.00183

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00176

AC:

ExAC

AF:

0.00273

AC:

330

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00385

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 22, 2018

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

Apr 10, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Arg5187His in exon 35 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 0.9% (264/30774) of South Asian c hromosomes and 1.6% (159/10110) of Ashkenazi Jewish chromosomes, including 4 hom ozygotes, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org; dbSNP rs201530874). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.3

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.013

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.95

PhyloP100

-1.4

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.070

REVEL

Benign

0.088

Sift

Benign

0.55

Vest4

0.26

MVP

0.23

ClinPred

0.011

GERP RS

0.68

Varity_R

0.031

gMVP

0.50

Mutation Taster

=98/2

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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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