chr11-1250278-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.13398G>A(p.Thr4466Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,611,090 control chromosomes in the GnomAD database, including 80,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7153 hom., cov: 30)

Exomes 𝑓: 0.31 ( 73293 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.38

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-1250278-G-A is Benign according to our data. Variant chr11-1250278-G-A is described in ClinVar as [Benign]. Clinvar id is 403176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.13398G>A	p.Thr4466Thr	synonymous_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.13398G>A	p.Thr4466Thr	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44186

AN:

149938

Hom.:

7138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.320

AC:

78854

AN:

246290

AF XY:

0.319

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.609

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.312

AC:

455742

AN:

1461032

Hom.:

73293

Cov.:

120

AF XY:

0.310

AC XY:

225537

AN XY:

726768

show subpopulations

African (AFR)

AF:

0.210

AC:

7028

AN:

33458

American (AMR)

AF:

0.303

AC:

13569

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7579

AN:

26130

East Asian (EAS)

AF:

0.594

AC:

23579

AN:

39694

South Asian (SAS)

AF:

0.281

AC:

24200

AN:

86238

European-Finnish (FIN)

AF:

0.282

AC:

14943

AN:

53046

Middle Eastern (MID)

AF:

0.287

AC:

1643

AN:

5732

European-Non Finnish (NFE)

AF:

0.310

AC:

344275

AN:

1111676

Other (OTH)

AF:

0.314

AC:

18926

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

26356

52712

79067

105423

131779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11340

22680

34020

45360

56700

<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:

0.295

AC:

44221

AN:

150058

Hom.:

7153

Cov.:

AF XY:

0.296

AC XY:

21642

AN XY:

73200

show subpopulations

African (AFR)

AF:

0.218

AC:

8908

AN:

40920

American (AMR)

AF:

0.329

AC:

4985

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1030

AN:

3442

East Asian (EAS)

AF:

0.597

AC:

3038

AN:

5088

South Asian (SAS)

AF:

0.292

AC:

1386

AN:

4748

European-Finnish (FIN)

AF:

0.286

AC:

2933

AN:

10266

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

20868

AN:

67148

Other (OTH)

AF:

0.320

AC:

668

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1490

2979

4469

5958

7448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.293

Hom.:

1170

Bravo

AF:

0.294

EpiCase

AF:

0.309

EpiControl

AF:

0.313

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

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

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.3

(source)

DANN

Benign

0.76

PhyloP100

-3.4

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