rs56179538

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.757G>A(p.Gly253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 717,660 control chromosomes in the GnomAD database, including 248 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 0.026 ( 171 hom., cov: 34)

Exomes 𝑓: 0.0047 ( 77 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.75

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002224356).

BP6

Variant 11-1227764-G-A is Benign according to our data. Variant chr11-1227764-G-A is described in ClinVar as Benign. ClinVar VariationId is 178784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.757G>A	p.Gly253Ser	missense_variant	Exon 7 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.757G>A	p.Gly253Ser	missense_variant	Exon 7 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.815G>A		non_coding_transcript_exon_variant	Exon 7 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3943

AN:

152204

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00750

AC:

1158

AN:

154466

AF XY:

0.00617

show subpopulations

Gnomad AFR exome

AF:

0.0945

Gnomad AMR exome

AF:

0.00843

Gnomad ASJ exome

AF:

0.00540

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00807

GnomAD4 exome

AF:

0.00470

AC:

2655

AN:

565338

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

1225

AN XY:

305038

show subpopulations

African (AFR)

AF:

0.0869

AC:

1381

AN:

15886

American (AMR)

AF:

0.00972

AC:

339

AN:

34880

Ashkenazi Jewish (ASJ)

AF:

0.00549

AC:

110

AN:

20032

East Asian (EAS)

AF:

0.0000311

AC:

AN:

32170

South Asian (SAS)

AF:

0.000924

AC:

AN:

62798

European-Finnish (FIN)

AF:

0.0000210

AC:

AN:

47714

Middle Eastern (MID)

AF:

0.0133

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.00120

AC:

381

AN:

317068

Other (OTH)

AF:

0.0107

AC:

330

AN:

30718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.0259

AC:

3950

AN:

152322

Hom.:

171

Cov.:

AF XY:

0.0244

AC XY:

1820

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0869

AC:

3610

AN:

41560

American (AMR)

AF:

0.0123

AC:

189

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

68034

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

187

375

562

750

937

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:

0.0116

Hom.:

Bravo

AF:

0.0300

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0701

AC:

259

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.00499

AC:

498

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 22, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Gly253Ser in exon 7 of MUC5B: This variant is not expected to have clinical sign ificance because it has been identified in 7.0% (259/3694) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs56179538). -

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

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.029

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.63

PhyloP100

-1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

0.55

REVEL

Benign

0.020

Sift

Benign

0.95

Polyphen

0.0

Vest4

0.11

MVP

0.043

ClinPred

0.00021

GERP RS

-5.1

Varity_R

0.027

gMVP

0.40

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