chr11-1250996-A-C

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.14116A>C(p.Thr4706Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,586,920 control chromosomes in the GnomAD database, including 214,695 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 0.52 ( 20589 hom., cov: 30)

Exomes 𝑓: 0.51 ( 194106 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.82

Publications

30 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=2.664287E-6).

BP6

Variant 11-1250996-A-C is Benign according to our data. Variant chr11-1250996-A-C is described in ClinVar as Benign. ClinVar VariationId is 403179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.14116A>C	p.Thr4706Pro	missense_variant	Exon 31 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.14116A>C	p.Thr4706Pro	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

76729

AN:

148530

Hom.:

20554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.520

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.527

GnomAD2 exomes

AF:

0.532

AC:

130899

AN:

246148

AF XY:

0.526

show subpopulations

Gnomad AFR exome

AF:

0.492

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.507

AC:

729107

AN:

1438268

Hom.:

194106

Cov.:

109

AF XY:

0.506

AC XY:

362192

AN XY:

715934

show subpopulations

African (AFR)

AF:

0.495

AC:

16488

AN:

33286

American (AMR)

AF:

0.615

AC:

27402

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

13557

AN:

25820

East Asian (EAS)

AF:

0.701

AC:

27805

AN:

39692

South Asian (SAS)

AF:

0.503

AC:

43215

AN:

85874

European-Finnish (FIN)

AF:

0.547

AC:

28731

AN:

52480

Middle Eastern (MID)

AF:

0.520

AC:

2996

AN:

5760

European-Non Finnish (NFE)

AF:

0.494

AC:

538613

AN:

1091184

Other (OTH)

AF:

0.508

AC:

30300

AN:

59628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

28363

56726

85088

113451

141814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15660

31320

46980

62640

78300

<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:

0.517

AC:

76814

AN:

148652

Hom.:

20589

Cov.:

AF XY:

0.522

AC XY:

37875

AN XY:

72526

show subpopulations

African (AFR)

AF:

0.500

AC:

20261

AN:

40544

American (AMR)

AF:

0.584

AC:

8853

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

1807

AN:

3412

East Asian (EAS)

AF:

0.664

AC:

3375

AN:

5086

South Asian (SAS)

AF:

0.508

AC:

2405

AN:

4734

European-Finnish (FIN)

AF:

0.565

AC:

5670

AN:

10036

Middle Eastern (MID)

AF:

0.500

AC:

143

AN:

286

European-Non Finnish (NFE)

AF:

0.492

AC:

32710

AN:

66434

Other (OTH)

AF:

0.531

AC:

1096

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1826

3652

5477

7303

9129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.457

Hom.:

4941

Bravo

AF:

0.516

TwinsUK

AF:

0.487

AC:

1805

ALSPAC

AF:

0.486

AC:

1873

ESP6500AA

AF:

0.463

AC:

1966

ESP6500EA

AF:

0.473

AC:

3991

ExAC

AF:

0.520

AC:

62813

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

0.064

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.027

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.030

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0000027

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

PhyloP100

-1.8

PrimateAI

Benign

0.25

PROVEAN

Benign

0.52

REVEL

Benign

0.083

Sift

Benign

1.0

Vest4

0.010

ClinPred

0.0019

GERP RS

-3.2

Varity_R

0.047

gMVP

0.14

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