NM_002458.3:c.16110C>A

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.16110C>A(p.Pro5370Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 734,482 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 31)

Exomes 𝑓: 0.028 ( 349 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.21

Publications

3 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=-0.77).

BP6

Variant 11-1256199-C-A is Benign according to our data. Variant chr11-1256199-C-A is described in ClinVar as Benign. ClinVar VariationId is 178797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.025 (3804/152218) while in subpopulation NFE AF = 0.0327 (2226/67980). AF 95% confidence interval is 0.0316. There are 63 homozygotes in GnomAd4. There are 1894 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.16110C>A	p.Pro5370Pro	synonymous_variant	Exon 38 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.16110C>A	p.Pro5370Pro	synonymous_variant	Exon 38 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0256

AC:

4636

AN:

181320

AF XY:

0.0250

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00537

Gnomad ASJ exome

AF:

0.0279

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0263

GnomAD4 exome

AF:

0.0278

AC:

16159

AN:

582264

Hom.:

349

Cov.:

AF XY:

0.0264

AC XY:

8332

AN XY:

315182

show subpopulations

African (AFR)

AF:

0.0125

AC:

202

AN:

16224

American (AMR)

AF:

0.00538

AC:

201

AN:

37372

Ashkenazi Jewish (ASJ)

AF:

0.0281

AC:

568

AN:

20242

East Asian (EAS)

AF:

0.00

AC:

AN:

32882

South Asian (SAS)

AF:

0.00972

AC:

621

AN:

63878

European-Finnish (FIN)

AF:

0.0722

AC:

3527

AN:

48868

Middle Eastern (MID)

AF:

0.00438

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.0312

AC:

10200

AN:

327214

Other (OTH)

AF:

0.0261

AC:

822

AN:

31472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

794

1589

2383

3178

3972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0250

AC:

3804

AN:

152218

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1894

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0131

AC:

543

AN:

41534

American (AMR)

AF:

0.00738

AC:

113

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00808

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0692

AC:

735

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0327

AC:

2226

AN:

67980

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

188

376

565

753

941

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:

0.0294

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Pro5370Pro in exon 38 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 2.8% (234/8374) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs55845452). -

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.028

(source)

DANN

Benign

0.70

PhyloP100

-4.2

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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