11-1229258-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.1065C>T(p.Cys355Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,586,682 control chromosomes in the GnomAD database, including 109,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10199 hom., cov: 33)

Exomes 𝑓: 0.37 ( 99316 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.118

Publications

32 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=-0.52).

BP6

Variant 11-1229258-C-T is Benign according to our data. Variant chr11-1229258-C-T is described in ClinVar as Benign. ClinVar VariationId is 178786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.1065C>T	p.Cys355Cys	synonymous_variant	Exon 9 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MUC5B	ENST00000529681.5 link	c.1065C>T	p.Cys355Cys	synonymous_variant	Exon 9 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5 link	n.1123C>T		non_coding_transcript_exon_variant	Exon 9 of 26	1
MUC5B	ENST00000531082.1 link	n.335C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54721

AN:

151892

Hom.:

10182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.371

GnomAD2 exomes

AF:

0.387

AC:

81495

AN:

210640

AF XY:

0.380

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.609

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.370

AC:

530320

AN:

1434672

Hom.:

99316

Cov.:

AF XY:

0.367

AC XY:

261566

AN XY:

712066

show subpopulations

African (AFR)

AF:

0.282

AC:

9269

AN:

32848

American (AMR)

AF:

0.450

AC:

18978

AN:

42132

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

8581

AN:

25636

East Asian (EAS)

AF:

0.596

AC:

22726

AN:

38146

South Asian (SAS)

AF:

0.330

AC:

27297

AN:

82718

European-Finnish (FIN)

AF:

0.364

AC:

16668

AN:

45818

Middle Eastern (MID)

AF:

0.330

AC:

1893

AN:

5738

European-Non Finnish (NFE)

AF:

0.366

AC:

403004

AN:

1102128

Other (OTH)

AF:

0.368

AC:

21904

AN:

59508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17937

35875

53812

71750

89687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12904

25808

38712

51616

64520

<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:

0.360

AC:

54771

AN:

152010

Hom.:

10199

Cov.:

AF XY:

0.364

AC XY:

27073

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.292

AC:

12100

AN:

41470

American (AMR)

AF:

0.443

AC:

6770

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3470

East Asian (EAS)

AF:

0.603

AC:

3102

AN:

5146

South Asian (SAS)

AF:

0.340

AC:

1639

AN:

4822

European-Finnish (FIN)

AF:

0.376

AC:

3975

AN:

10578

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24722

AN:

67928

Other (OTH)

AF:

0.378

AC:

796

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1781

3561

5342

7122

8903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.364

Hom.:

25148

Bravo

AF:

0.364

Asia WGS

AF:

0.510

AC:

1773

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

- -

Jun 09, 2021

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

Cys355Cys in exon 9 of MUC5B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 34.7% (2915/8394) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2075859). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.53

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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