chr11-1251598-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.14718T>C(p.Pro4906Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,612,970 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 50 hom., cov: 33)

Exomes 𝑓: 0.028 ( 732 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.85

Publications

2 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=-1.0).

BP6

Variant 11-1251598-T-C is Benign according to our data. Variant chr11-1251598-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 403198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0212 (3224/152332) while in subpopulation NFE AF = 0.0299 (2033/68018). AF 95% confidence interval is 0.0288. There are 50 homozygotes in GnomAd4. There are 1626 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.14718T>C	p.Pro4906Pro	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.14718T>C	p.Pro4906Pro	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3223

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0240

AC:

5940

AN:

247506

AF XY:

0.0241

show subpopulations

Gnomad AFR exome

AF:

0.00574

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0737

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0276

AC:

40301

AN:

1460638

Hom.:

732

Cov.:

AF XY:

0.0270

AC XY:

19632

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.00341

AC:

114

AN:

33476

American (AMR)

AF:

0.00499

AC:

223

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

632

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00936

AC:

807

AN:

86252

European-Finnish (FIN)

AF:

0.0715

AC:

3753

AN:

52512

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0299

AC:

33270

AN:

1111758

Other (OTH)

AF:

0.0245

AC:

1477

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2599

5198

7796

10395

12994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1226

2452

3678

4904

6130

<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:

0.0212

AC:

3224

AN:

152332

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1626

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00500

AC:

208

AN:

41576

American (AMR)

AF:

0.00653

AC:

100

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00807

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0684

AC:

727

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2033

AN:

68018

Other (OTH)

AF:

0.0189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0259

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0247

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.30

(source)

DANN

Benign

0.27

PhyloP100

-7.9

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