chr11-1231478-G-C

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.1596G>C(p.Leu532Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,608,528 control chromosomes in the GnomAD database, including 218,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22954 hom., cov: 34)

Exomes 𝑓: 0.52 ( 195918 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.09

Publications

20 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=-0.9).

BP6

Variant 11-1231478-G-C is Benign according to our data. Variant chr11-1231478-G-C is described in ClinVar as Benign. ClinVar VariationId is 163995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.1596G>C	p.Leu532Leu	synonymous_variant	Exon 14 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.1596G>C	p.Leu532Leu	synonymous_variant	Exon 14 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.1654G>C		non_coding_transcript_exon_variant	Exon 14 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

83072

AN:

152022

Hom.:

22922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.552

GnomAD2 exomes

AF:

0.544

AC:

131192

AN:

240944

AF XY:

0.537

show subpopulations

Gnomad AFR exome

AF:

0.574

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.517

AC:

752531

AN:

1456388

Hom.:

195918

Cov.:

AF XY:

0.515

AC XY:

373176

AN XY:

724264

show subpopulations

African (AFR)

AF:

0.577

AC:

19286

AN:

33396

American (AMR)

AF:

0.619

AC:

27254

AN:

44052

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

14094

AN:

26056

East Asian (EAS)

AF:

0.701

AC:

27680

AN:

39488

South Asian (SAS)

AF:

0.503

AC:

43121

AN:

85706

European-Finnish (FIN)

AF:

0.575

AC:

29743

AN:

51736

Middle Eastern (MID)

AF:

0.529

AC:

3051

AN:

5764

European-Non Finnish (NFE)

AF:

0.502

AC:

556839

AN:

1109998

Other (OTH)

AF:

0.523

AC:

31463

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

19502

39005

58507

78010

97512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16354

32708

49062

65416

81770

<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:

0.547

AC:

83158

AN:

152140

Hom.:

22954

Cov.:

AF XY:

0.552

AC XY:

41056

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.577

AC:

23969

AN:

41508

American (AMR)

AF:

0.599

AC:

9153

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.548

AC:

1901

AN:

3470

East Asian (EAS)

AF:

0.662

AC:

3426

AN:

5176

South Asian (SAS)

AF:

0.505

AC:

2435

AN:

4822

European-Finnish (FIN)

AF:

0.588

AC:

6232

AN:

10592

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34223

AN:

67968

Other (OTH)

AF:

0.555

AC:

1174

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2028

4056

6085

8113

10141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.447

Hom.:

2236

Bravo

AF:

0.551

Asia WGS

AF:

0.622

AC:

2161

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

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu532Leu in exon 14 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 49.8% (4172/8376) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2735709). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.40

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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