11-1250199-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.13319C>T(p.Pro4440Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,579,942 control chromosomes in the GnomAD database, including 162,493 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 0.43 ( 14315 hom., cov: 30)

Exomes 𝑓: 0.45 ( 148178 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.11

Publications

20 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=1.3935443E-5).

BP6

Variant 11-1250199-C-T is Benign according to our data. Variant chr11-1250199-C-T is described in ClinVar as [Benign]. Clinvar id is 403175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.13319C>T	p.Pro4440Leu	missense_variant	Exon 31 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.13319C>T	p.Pro4440Leu	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

63369

AN:

147664

Hom.:

14297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.443

GnomAD2 exomes

AF:

0.482

AC:

116825

AN:

242498

AF XY:

0.475

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.657

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.455

AC:

651171

AN:

1432162

Hom.:

148178

Cov.:

140

AF XY:

0.453

AC XY:

322953

AN XY:

712838

show subpopulations

African (AFR)

AF:

0.316

AC:

10532

AN:

33280

American (AMR)

AF:

0.582

AC:

25938

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

11106

AN:

25712

East Asian (EAS)

AF:

0.697

AC:

27651

AN:

39690

South Asian (SAS)

AF:

0.425

AC:

36478

AN:

85746

European-Finnish (FIN)

AF:

0.510

AC:

26199

AN:

51380

Middle Eastern (MID)

AF:

0.429

AC:

2459

AN:

5728

European-Non Finnish (NFE)

AF:

0.446

AC:

484133

AN:

1086536

Other (OTH)

AF:

0.448

AC:

26675

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

31005

62010

93016

124021

155026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14810

29620

44430

59240

74050

<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:

0.429

AC:

63413

AN:

147780

Hom.:

14315

Cov.:

AF XY:

0.438

AC XY:

31535

AN XY:

72076

show subpopulations

African (AFR)

AF:

0.321

AC:

13043

AN:

40658

American (AMR)

AF:

0.533

AC:

8046

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1492

AN:

3380

East Asian (EAS)

AF:

0.646

AC:

3214

AN:

4976

South Asian (SAS)

AF:

0.429

AC:

2022

AN:

4714

European-Finnish (FIN)

AF:

0.526

AC:

5192

AN:

9870

Middle Eastern (MID)

AF:

0.369

AC:

107

AN:

290

European-Non Finnish (NFE)

AF:

0.439

AC:

28902

AN:

65848

Other (OTH)

AF:

0.448

AC:

925

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1639

3279

4918

6558

8197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.389

Hom.:

2551

Bravo

AF:

0.425

ESP6500AA

AF:

0.303

AC:

1253

ESP6500EA

AF:

0.430

AC:

3605

ExAC

AF:

0.474

AC:

57281

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

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.3

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.019

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.56

MetaRNN

Benign

0.000014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-2.1

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.52

REVEL

Benign

0.025

Sift

Benign

0.30

Vest4

0.023

ClinPred

0.0025

GERP RS

-0.047

Varity_R

0.022

gMVP

0.34

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