rs2943517

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.13211C>G(p.Ala4404Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,610,152 control chromosomes in the GnomAD database, including 159,555 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13744 hom., cov: 30)

Exomes 𝑓: 0.44 ( 145811 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.209

Publications

27 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=1.7681718E-4).

BP6

Variant 11-1250091-C-G is Benign according to our data. Variant chr11-1250091-C-G is described in ClinVar as [Benign]. Clinvar id is 403174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.13211C>G	p.Ala4404Gly	missense_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.13211C>G	p.Ala4404Gly	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

63651

AN:

150322

Hom.:

13728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.440

GnomAD2 exomes

AF:

0.469

AC:

115850

AN:

246994

AF XY:

0.463

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.624

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.443

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.445

AC:

648945

AN:

1459718

Hom.:

145811

Cov.:

117

AF XY:

0.443

AC XY:

321912

AN XY:

726116

show subpopulations

African (AFR)

AF:

0.301

AC:

10056

AN:

33368

American (AMR)

AF:

0.582

AC:

26004

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

10954

AN:

26110

East Asian (EAS)

AF:

0.677

AC:

26662

AN:

39370

South Asian (SAS)

AF:

0.421

AC:

36191

AN:

86048

European-Finnish (FIN)

AF:

0.491

AC:

26015

AN:

52998

Middle Eastern (MID)

AF:

0.431

AC:

2486

AN:

5762

European-Non Finnish (NFE)

AF:

0.436

AC:

484187

AN:

1111120

Other (OTH)

AF:

0.438

AC:

26390

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

29556

59113

88669

118226

147782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.423

AC:

63691

AN:

150434

Hom.:

13744

Cov.:

AF XY:

0.431

AC XY:

31663

AN XY:

73416

show subpopulations

African (AFR)

AF:

0.313

AC:

12849

AN:

41042

American (AMR)

AF:

0.534

AC:

8109

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1487

AN:

3458

East Asian (EAS)

AF:

0.624

AC:

3036

AN:

4868

South Asian (SAS)

AF:

0.428

AC:

2028

AN:

4742

European-Finnish (FIN)

AF:

0.510

AC:

5288

AN:

10378

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.435

AC:

29377

AN:

67476

Other (OTH)

AF:

0.445

AC:

926

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.429

Hom.:

3488

ExAC

AF:

0.458

AC:

55204

EpiCase

AF:

0.438

EpiControl

AF:

0.437

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.015

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.34

MetaRNN

Benign

0.00018

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-0.21

PrimateAI

Benign

0.18

PROVEAN

Benign

0.030

REVEL

Benign

0.037

Sift

Benign

0.41

Vest4

0.018

ClinPred

0.012

GERP RS

-0.67

Varity_R

0.027

gMVP

0.19

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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rs2943517

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