11-1234543-C-T

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.2493C>T(p.Cys831Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,579,296 control chromosomes in the GnomAD database, including 78,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6980 hom., cov: 30)

Exomes 𝑓: 0.31 ( 71327 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.659

Publications

15 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=-0.62).

BP6

Variant 11-1234543-C-T is Benign according to our data. Variant chr11-1234543-C-T is described in ClinVar as Benign. ClinVar VariationId is 163998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.659 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.2493C>T	p.Cys831Cys	synonymous_variant	Exon 21 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.2493C>T	p.Cys831Cys	synonymous_variant	Exon 21 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.2551C>T		non_coding_transcript_exon_variant	Exon 21 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44525

AN:

151726

Hom.:

6966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.311

AC:

60954

AN:

195868

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.312

AC:

444827

AN:

1427450

Hom.:

71327

Cov.:

AF XY:

0.310

AC XY:

218954

AN XY:

706700

show subpopulations

African (AFR)

AF:

0.209

AC:

6848

AN:

32796

American (AMR)

AF:

0.302

AC:

12118

AN:

40180

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

7528

AN:

25432

East Asian (EAS)

AF:

0.591

AC:

22256

AN:

37636

South Asian (SAS)

AF:

0.279

AC:

22636

AN:

81216

European-Finnish (FIN)

AF:

0.281

AC:

13998

AN:

49842

Middle Eastern (MID)

AF:

0.286

AC:

1634

AN:

5710

European-Non Finnish (NFE)

AF:

0.310

AC:

339233

AN:

1095512

Other (OTH)

AF:

0.314

AC:

18576

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

17447

34895

52342

69790

87237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11252

22504

33756

45008

56260

<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:

0.293

AC:

44560

AN:

151846

Hom.:

6980

Cov.:

AF XY:

0.295

AC XY:

21881

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.215

AC:

8920

AN:

41410

American (AMR)

AF:

0.331

AC:

5060

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1055

AN:

3470

East Asian (EAS)

AF:

0.599

AC:

3087

AN:

5156

South Asian (SAS)

AF:

0.290

AC:

1391

AN:

4802

European-Finnish (FIN)

AF:

0.281

AC:

2965

AN:

10564

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.309

AC:

21003

AN:

67874

Other (OTH)

AF:

0.320

AC:

675

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1566

3132

4697

6263

7829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.297

Hom.:

3207

Bravo

AF:

0.295

Asia WGS

AF:

0.481

AC:

1670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cys831Cys in exon 21 of MUC5B: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 28.9% (2440/8444) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7116614). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.2

(source)

DANN

Benign

0.67

PhyloP100

-0.66

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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