11-1245369-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.8489C>T(p.Pro2830Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,568,878 control chromosomes in the GnomAD database, including 54,294 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 0.14 ( 3022 hom., cov: 21)

Exomes 𝑓: 0.19 ( 51272 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.74

Publications

7 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 links:

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 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=0.0060741007).

BP6

Variant 11-1245369-C-T is Benign according to our data. Variant chr11-1245369-C-T is described in ClinVar as Benign. ClinVar VariationId is 403146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.8489C>T	p.Pro2830Leu	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 link	n.57-2731G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.8489C>T	p.Pro2830Leu	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2 link	n.57-2731G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

19212

AN:

137856

Hom.:

3019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.00502

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.132

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.137

GnomAD2 exomes

AF:

0.166

AC:

39772

AN:

239792

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.00329

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.191

AC:

272927

AN:

1430906

Hom.:

51272

Cov.:

106

AF XY:

0.191

AC XY:

135906

AN XY:

712088

show subpopulations

African (AFR)

AF:

0.0300

AC:

992

AN:

33042

American (AMR)

AF:

0.100

AC:

4173

AN:

41690

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4305

AN:

25648

East Asian (EAS)

AF:

0.00198

AC:

AN:

39378

South Asian (SAS)

AF:

0.165

AC:

13900

AN:

84258

European-Finnish (FIN)

AF:

0.233

AC:

11799

AN:

50634

Middle Eastern (MID)

AF:

0.171

AC:

695

AN:

4058

European-Non Finnish (NFE)

AF:

0.207

AC:

226416

AN:

1093022

Other (OTH)

AF:

0.179

AC:

10569

AN:

59176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

13182

26363

39545

52726

65908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7006

14012

21018

28024

35030

<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:

0.139

AC:

19216

AN:

137972

Hom.:

3022

Cov.:

AF XY:

0.141

AC XY:

9392

AN XY:

66548

show subpopulations

African (AFR)

AF:

0.0351

AC:

1340

AN:

38168

American (AMR)

AF:

0.127

AC:

1683

AN:

13288

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

518

AN:

3246

East Asian (EAS)

AF:

0.00503

AC:

AN:

4968

South Asian (SAS)

AF:

0.152

AC:

615

AN:

4044

European-Finnish (FIN)

AF:

0.255

AC:

2152

AN:

8450

Middle Eastern (MID)

AF:

0.143

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.198

AC:

12410

AN:

62798

Other (OTH)

AF:

0.139

AC:

265

AN:

1910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

576

1152

1727

2303

2879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.163

Hom.:

762

ESP6500AA

AF:

0.0401

AC:

162

ESP6500EA

AF:

0.209

AC:

1706

ExAC

AF:

0.166

AC:

19621

Asia WGS

AF:

0.0740

AC:

256

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.069

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.020

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-3.7

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.73

Sift

Benign

0.058

Vest4

0.011

ClinPred

0.00065

GERP RS

-0.90

Varity_R

0.028

gMVP

0.42

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