11-1242527-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.5647A>G(p.Ser1883Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,613,698 control chromosomes in the GnomAD database, including 913 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 0.025 ( 63 hom., cov: 32)

Exomes 𝑓: 0.030 ( 850 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.80

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002051562).

BP6

Variant 11-1242527-A-G is Benign according to our data. Variant chr11-1242527-A-G is described in ClinVar as Benign. ClinVar VariationId is 403130.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 = 0.0251 (3823/152086) while in subpopulation NFE AF = 0.0327 (2221/67964). AF 95% confidence interval is 0.0315. There are 63 homozygotes in GnomAd4. There are 1898 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.5647A>G	p.Ser1883Gly	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.168T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.5647A>G	p.Ser1883Gly	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.168T>C		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3822

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

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:

0.0268

AC:

6680

AN:

249352

AF XY:

0.0266

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.00516

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.0345

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0302

AC:

44149

AN:

1461612

Hom.:

850

Cov.:

AF XY:

0.0295

AC XY:

21483

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.0122

AC:

410

AN:

33480

American (AMR)

AF:

0.00577

AC:

258

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

763

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00953

AC:

822

AN:

86258

European-Finnish (FIN)

AF:

0.0728

AC:

3886

AN:

53388

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0327

AC:

36321

AN:

1111814

Other (OTH)

AF:

0.0275

AC:

1662

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

3360

6720

10081

13441

16801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1334

2668

4002

5336

6670

<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:

0.0251

AC:

3823

AN:

152086

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1898

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0137

AC:

568

AN:

41454

American (AMR)

AF:

0.00746

AC:

114

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00809

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0692

AC:

733

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0327

AC:

2221

AN:

67964

Other (OTH)

AF:

0.0223

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

184

367

551

734

918

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:

0.0281

Hom.:

214

Bravo

AF:

0.0200

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0330

AC:

127

ESP6500AA

AF:

0.0162

AC:

ESP6500EA

AF:

0.0328

AC:

281

ExAC

AF:

0.0279

AC:

3385

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0251

EpiControl

AF:

0.0265

ClinVar

Significance: 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: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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.022

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.037

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-1.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.2

REVEL

Benign

0.0090

Sift

Benign

0.18

Vest4

0.036

ClinPred

0.0017

GERP RS

-0.31

Varity_R

0.052

gMVP

0.63

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