NM_002458.3:c.15972T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.15972T>C(p.Leu5324Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,537,202 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 64 hom., cov: 31)

Exomes 𝑓: 0.011 ( 349 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.64

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 11-1255464-T-C is Benign according to our data. Variant chr11-1255464-T-C is described in ClinVar as Benign. ClinVar VariationId is 178795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.64 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3774/151982) while in subpopulation NFE AF = 0.0325 (2206/67880). AF 95% confidence interval is 0.0314. There are 64 homozygotes in GnomAd4. There are 1873 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.15972T>C	p.Leu5324Leu	synonymous_variant	Exon 37 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.15972T>C	p.Leu5324Leu	synonymous_variant	Exon 37 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3775

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0689

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0124

AC:

2577

AN:

207460

AF XY:

0.0118

show subpopulations

Gnomad AFR exome

AF:

0.00979

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00668

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0147

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.0106

AC:

14721

AN:

1385220

Hom.:

349

Cov.:

AF XY:

0.0109

AC XY:

7504

AN XY:

688922

show subpopulations

African (AFR)

AF:

0.00538

AC:

175

AN:

32542

American (AMR)

AF:

0.00317

AC:

133

AN:

41972

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

407

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

38534

South Asian (SAS)

AF:

0.00570

AC:

471

AN:

82596

European-Finnish (FIN)

AF:

0.0653

AC:

3243

AN:

49654

Middle Eastern (MID)

AF:

0.00262

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00907

AC:

9536

AN:

1051256

Other (OTH)

AF:

0.0128

AC:

741

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

833

1667

2500

3334

4167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0248

AC:

3774

AN:

151982

Hom.:

Cov.:

AF XY:

0.0252

AC XY:

1873

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0130

AC:

538

AN:

41468

American (AMR)

AF:

0.00746

AC:

114

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00809

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0689

AC:

730

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0325

AC:

2206

AN:

67880

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

194

388

581

775

969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0268

Hom.:

Bravo

AF:

0.0198

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 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MUC5B: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu5324Leu in exon 37 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 3.1% (256/8274) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56229218). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.12

(source)

DANN

Benign

0.29

PhyloP100

-2.6

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