Genetic Variant MUC5B:p.His311His (chr11-1228722-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002458.3(MUC5B):c.933C>T(p.His311His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,524,960 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0050 ( 28 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 11-1228722-C-T is Benign according to our data. Variant chr11-1228722-C-T is described in ClinVar as Benign. ClinVar VariationId is 178785.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.933C>T	p.His311His	synonymous_variant	Exon 8 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MUC5B	ENST00000529681.5 link	c.933C>T	p.His311His	synonymous_variant	Exon 8 of 49	5	NM_002458.3	ENSP00000436812.1	Q9HC84
MUC5B	ENST00000525715.5 link	n.991C>T		non_coding_transcript_exon_variant	Exon 8 of 26	1
MUC5B	ENST00000531082.1 link	n.203C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00465

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00455

AC:

613

AN:

134602

AF XY:

0.00420

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.0000939

Gnomad FIN exome

AF:

0.00279

Gnomad NFE exome

AF:

0.00534

Gnomad OTH exome

AF:

0.00688

GnomAD4 exome

AF:

0.00498

AC:

6831

AN:

1372686

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3321

AN XY:

675234

show subpopulations

African (AFR)

AF:

0.0112

AC:

350

AN:

31356

American (AMR)

AF:

0.00374

AC:

132

AN:

35326

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

407

AN:

24968

East Asian (EAS)

AF:

0.0000565

AC:

AN:

35428

South Asian (SAS)

AF:

0.0000889

AC:

AN:

78702

European-Finnish (FIN)

AF:

0.00279

AC:

AN:

35078

Middle Eastern (MID)

AF:

0.000495

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.00512

AC:

5479

AN:

1070712

Other (OTH)

AF:

0.00620

AC:

354

AN:

57072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

397

794

1190

1587

1984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.00648

AC:

986

AN:

152274

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0115

AC:

478

AN:

41560

American (AMR)

AF:

0.00516

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00465

AC:

316

AN:

68014

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00463

Hom.:

Bravo

AF:

0.00681

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

His311His in exon 8 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 0.8% (28/3324) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs145446448). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.12

(source)

DANN

Benign

0.93

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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