11-1255237-A-G

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.15861A>G(p.Pro5287Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,151,180 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 59 hom., cov: 18)

Exomes 𝑓: 0.037 ( 765 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -7.33

Publications

6 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=-1.04).

BP6

Variant 11-1255237-A-G is Benign according to our data. Variant chr11-1255237-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.15861A>G	p.Pro5287Pro	synonymous_variant	Exon 36 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.15861A>G	p.Pro5287Pro	synonymous_variant	Exon 36 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

3680

AN:

65764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.000449

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0550

GnomAD2 exomes

AF:

0.0237

AC:

3335

AN:

141004

AF XY:

0.0231

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0712

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0369

AC:

40072

AN:

1085376

Hom.:

765

Cov.:

AF XY:

0.0361

AC XY:

19280

AN XY:

534404

show subpopulations

African (AFR)

AF:

0.0151

AC:

359

AN:

23804

American (AMR)

AF:

0.00710

AC:

204

AN:

28746

Ashkenazi Jewish (ASJ)

AF:

0.0424

AC:

688

AN:

16214

East Asian (EAS)

AF:

0.00

AC:

AN:

15694

South Asian (SAS)

AF:

0.00992

AC:

719

AN:

72500

European-Finnish (FIN)

AF:

0.107

AC:

3396

AN:

31828

Middle Eastern (MID)

AF:

0.00601

AC:

AN:

4328

European-Non Finnish (NFE)

AF:

0.0390

AC:

33209

AN:

851466

Other (OTH)

AF:

0.0361

AC:

1471

AN:

40796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

1806

3612

5417

7223

9029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1250

2500

3750

5000

6250

<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:

0.0559

AC:

3679

AN:

65804

Hom.:

Cov.:

AF XY:

0.0582

AC XY:

1819

AN XY:

31268

show subpopulations

African (AFR)

AF:

0.0324

AC:

519

AN:

16008

American (AMR)

AF:

0.0258

AC:

112

AN:

4340

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

AN:

1826

East Asian (EAS)

AF:

0.000450

AC:

AN:

2220

South Asian (SAS)

AF:

0.0218

AC:

AN:

1698

European-Finnish (FIN)

AF:

0.200

AC:

690

AN:

3444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.0624

AC:

2174

AN:

34866

Other (OTH)

AF:

0.0548

AC:

AN:

840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

170

341

511

682

852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0288

Hom.:

157

Bravo

AF:

0.0198

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro5287Pro in exon 36 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 7.0% (13/186) of F innish chromosomes from a broad population by the 1000 Genomes Project (http://w ww.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs56344012). -

Jun 03, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

-1.0

CADD

Benign

0.0030

(source)

DANN

Benign

0.17

PhyloP100

-7.3

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