rs200811033

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_002458.3(MUC5B):c.8900A>G(p.Asn2967Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,612,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 0 hom., cov: 28)

Exomes 𝑓: 0.030 ( 0 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

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 links:

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PM2

Variant has high frequency in the NFE (0.0318) population. However there is too low homozygotes in high coverage region: (expected more than 341, got 0).

BP4

Computational evidence support a benign effect (MetaRNN=0.0020525157).

BP6

Variant 11-1245780-A-G is Benign according to our data. Variant chr11-1245780-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 403184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0245 (3710/151184) while in subpopulation NFE AF = 0.0323 (2188/67844). AF 95% confidence interval is 0.0311. There are 0 homozygotes in GnomAd4. There are 1853 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.8900A>G	p.Asn2967Ser	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 link	n.57-3142T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.8900A>G	p.Asn2967Ser	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2 link	n.57-3142T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3711

AN:

151066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00750

Gnomad ASJ

AF:

0.0278

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00815

Gnomad FIN

AF:

0.0681

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0322

Gnomad OTH

AF:

0.0226

GnomAD2 exomes

AF:

0.0261

AC:

6489

AN:

248850

AF XY:

0.0258

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0720

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0296

AC:

43214

AN:

1461270

Hom.:

Cov.:

AF XY:

0.0290

AC XY:

21050

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.0111

AC:

370

AN:

33418

American (AMR)

AF:

0.00559

AC:

250

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

755

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00933

AC:

805

AN:

86248

European-Finnish (FIN)

AF:

0.0702

AC:

3733

AN:

53212

Middle Eastern (MID)

AF:

0.00474

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0321

AC:

35651

AN:

1111810

Other (OTH)

AF:

0.0269

AC:

1623

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

3716

7431

11147

14862

18578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

1332

2664

3996

5328

6660

<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:

0.0245

AC:

3710

AN:

151184

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1853

AN XY:

73872

show subpopulations

African (AFR)

AF:

0.0123

AC:

504

AN:

40878

American (AMR)

AF:

0.00749

AC:

114

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0278

AC:

AN:

3458

East Asian (EAS)

AF:

0.000195

AC:

AN:

5120

South Asian (SAS)

AF:

0.00816

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.0681

AC:

720

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2188

AN:

67844

Other (OTH)

AF:

0.0224

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

189

378

566

755

944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0277

Hom.:

ESP6500AA

AF:

0.0105

AC:

ESP6500EA

AF:

0.0311

AC:

256

ExAC

AF:

0.0273

AC:

3297

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely 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 -

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

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.022

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.92

REVEL

Benign

0.020

Sift

Benign

0.44

Vest4

0.068

ClinPred

0.0014

GERP RS

0.66

Varity_R

0.030

gMVP

0.76

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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