11-1250937-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.14057C>T(p.Thr4686Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,604,624 control chromosomes in the GnomAD database, including 6,301 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 0.061 ( 377 hom., cov: 31)

Exomes 𝑓: 0.086 ( 5924 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.268

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=0.0026409924).

BP6

Variant 11-1250937-C-T is Benign according to our data. Variant chr11-1250937-C-T is described in ClinVar as [Benign]. Clinvar id is 403178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.14057C>T	p.Thr4686Met	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.14057C>T	p.Thr4686Met	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9182

AN:

151556

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.0932

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.0618

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0576

GnomAD2 exomes

AF:

0.0679

AC:

15655

AN:

230652

AF XY:

0.0730

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0911

Gnomad EAS exome

AF:

0.000896

Gnomad FIN exome

AF:

0.0630

Gnomad NFE exome

AF:

0.0888

Gnomad OTH exome

AF:

0.0678

GnomAD4 exome

AF:

0.0859

AC:

124858

AN:

1452950

Hom.:

5924

Cov.:

142

AF XY:

0.0866

AC XY:

62569

AN XY:

722160

show subpopulations

African (AFR)

AF:

0.0134

AC:

443

AN:

33114

American (AMR)

AF:

0.0311

AC:

1342

AN:

43182

Ashkenazi Jewish (ASJ)

AF:

0.0875

AC:

2273

AN:

25990

East Asian (EAS)

AF:

0.000662

AC:

AN:

39288

South Asian (SAS)

AF:

0.0955

AC:

8179

AN:

85638

European-Finnish (FIN)

AF:

0.0605

AC:

3181

AN:

52554

Middle Eastern (MID)

AF:

0.0748

AC:

431

AN:

5762

European-Non Finnish (NFE)

AF:

0.0940

AC:

104079

AN:

1107370

Other (OTH)

AF:

0.0817

AC:

4904

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8196

16393

24589

32786

40982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0605

AC:

9179

AN:

151674

Hom.:

377

Cov.:

AF XY:

0.0591

AC XY:

4381

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.0161

AC:

666

AN:

41420

American (AMR)

AF:

0.0450

AC:

687

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0932

AC:

323

AN:

3464

East Asian (EAS)

AF:

0.00174

AC:

AN:

5174

South Asian (SAS)

AF:

0.0883

AC:

424

AN:

4802

European-Finnish (FIN)

AF:

0.0618

AC:

648

AN:

10486

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0914

AC:

6192

AN:

67748

Other (OTH)

AF:

0.0570

AC:

120

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

428

856

1285

1713

2141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0772

Hom.:

249

Bravo

AF:

0.0559

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.0932

AC:

767

ExAC

AF:

0.0666

AC:

8008

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.033

Eigen

Benign

-0.80

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.99

PhyloP100

0.27

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.47

REVEL

Benign

0.046

Sift

Benign

0.28

Vest4

0.046

ClinPred

0.0033

GERP RS

-0.97

Varity_R

0.020

gMVP

0.28

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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11-1250937-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