rs56220864

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.16422G>C(p.Glu5474Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,570,458 control chromosomes in the GnomAD database, including 840 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 64 hom., cov: 32)

Exomes 𝑓: 0.030 ( 776 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.566

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026461482).

BP6

Variant 11-1257682-G-C is Benign according to our data. Variant chr11-1257682-G-C is described in ClinVar as Benign. ClinVar VariationId is 164010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.025 (3806/152334) while in subpopulation NFE AF = 0.0327 (2227/68018). AF 95% confidence interval is 0.0316. There are 64 homozygotes in GnomAd4. There are 1891 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.16422G>C	p.Glu5474Asp	missense	Exon 41 of 49	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.16422G>C	p.Glu5474Asp	missense	Exon 41 of 49	ENSP00000436812.1
	MUC5B	ENST00000526859.1	TSL:3	c.57G>C	p.Glu19Asp	missense	Exon 1 of 6	ENSP00000434539.1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3807

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0231

AC:

4288

AN:

185316

AF XY:

0.0228

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.00517

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0684

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0296

AC:

41927

AN:

1418124

Hom.:

776

Cov.:

AF XY:

0.0289

AC XY:

20302

AN XY:

703558

show subpopulations

African (AFR)

AF:

0.0118

AC:

387

AN:

32708

American (AMR)

AF:

0.00560

AC:

223

AN:

39814

Ashkenazi Jewish (ASJ)

AF:

0.0287

AC:

735

AN:

25596

East Asian (EAS)

AF:

0.00

AC:

AN:

37844

South Asian (SAS)

AF:

0.00950

AC:

784

AN:

82498

European-Finnish (FIN)

AF:

0.0703

AC:

2609

AN:

37122

Middle Eastern (MID)

AF:

0.00472

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0324

AC:

35586

AN:

1097640

Other (OTH)

AF:

0.0266

AC:

1576

AN:

59184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2368

4736

7105

9473

11841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1324

2648

3972

5296

6620

<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:

0.0250

AC:

3806

AN:

152334

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1891

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0131

AC:

544

AN:

41584

American (AMR)

AF:

0.00745

AC:

114

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00788

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0692

AC:

735

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0327

AC:

2227

AN:

68018

Other (OTH)

AF:

0.0222

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

181

362

543

724

905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0308

Hom.:

Bravo

AF:

0.0198

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0330

AC:

127

ESP6500AA

AF:

0.0156

AC:

ESP6500EA

AF:

0.0300

AC:

247

ExAC

AF:

0.0214

AC:

2526

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.014

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.98

PhyloP100

-0.57

PrimateAI

Benign

0.33

PROVEAN

Benign

0.94

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.012

ClinPred

0.0036

GERP RS

3.0

PromoterAI

0.021

Neutral

(source)

Varity_R

0.033

gMVP

0.74

Mutation Taster

=99/1

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over