rs2075855

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.723G>A(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 723,098 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 345 hom., cov: 34)

Exomes 𝑓: 0.077 ( 1949 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.20

Publications

12 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=-0.75).

BP6

Variant 11-1227730-G-A is Benign according to our data. Variant chr11-1227730-G-A is described in ClinVar as Benign. ClinVar VariationId is 178783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.723G>A	p.Thr241Thr	synonymous_variant	Exon 7 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.723G>A	p.Thr241Thr	synonymous_variant	Exon 7 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.781G>A		non_coding_transcript_exon_variant	Exon 7 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.0621

AC:

9455

AN:

152176

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0891

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0679

GnomAD2 exomes

AF:

0.0792

AC:

12912

AN:

163074

AF XY:

0.0786

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.0836

Gnomad EAS exome

AF:

0.0453

Gnomad FIN exome

AF:

0.0999

Gnomad NFE exome

AF:

0.0697

Gnomad OTH exome

AF:

0.0765

GnomAD4 exome

AF:

0.0773

AC:

44102

AN:

570804

Hom.:

1949

Cov.:

AF XY:

0.0774

AC XY:

23857

AN XY:

308344

show subpopulations

African (AFR)

AF:

0.0292

AC:

469

AN:

16062

American (AMR)

AF:

0.121

AC:

4296

AN:

35478

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

1701

AN:

20124

East Asian (EAS)

AF:

0.108

AC:

3509

AN:

32472

South Asian (SAS)

AF:

0.0796

AC:

5022

AN:

63090

European-Finnish (FIN)

AF:

0.101

AC:

4882

AN:

48132

Middle Eastern (MID)

AF:

0.0933

AC:

381

AN:

4084

European-Non Finnish (NFE)

AF:

0.0678

AC:

21720

AN:

320388

Other (OTH)

AF:

0.0685

AC:

2122

AN:

30974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2154

4308

6463

8617

10771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.0620

AC:

9448

AN:

152294

Hom.:

345

Cov.:

AF XY:

0.0649

AC XY:

4830

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0277

AC:

1151

AN:

41570

American (AMR)

AF:

0.0889

AC:

1360

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

319

AN:

3472

East Asian (EAS)

AF:

0.0522

AC:

270

AN:

5170

South Asian (SAS)

AF:

0.0792

AC:

382

AN:

4826

European-Finnish (FIN)

AF:

0.105

AC:

1118

AN:

10624

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0675

AC:

4593

AN:

68010

Other (OTH)

AF:

0.0667

AC:

141

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

478

957

1435

1914

2392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0651

Hom.:

148

Bravo

AF:

0.0607

Asia WGS

AF:

0.0540

AC:

188

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

Thr241Thr in exon 7 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 6.0% (483/8038) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs2075855). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.059

(source)

DANN

Benign

0.73

PhyloP100

-3.2

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