rs2943521

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.11725G>A(p.Val3909Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,609,662 control chromosomes in the GnomAD database, including 163,161 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V3909A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.43 ( 14462 hom., cov: 28)

Exomes 𝑓: 0.45 ( 148699 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.04

Publications

16 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=6.6728385E-6).

BP6

Variant 11-1248605-G-A is Benign according to our data. Variant chr11-1248605-G-A is described in ClinVar as Benign. ClinVar VariationId is 403171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.11725G>A	p.Val3909Ile	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+1016C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.11725G>A	p.Val3909Ile	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+1016C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

64766

AN:

150336

Hom.:

14445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.537

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.443

GnomAD2 exomes

AF:

0.469

AC:

113204

AN:

241520

AF XY:

0.462

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.590

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.660

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.446

AC:

651299

AN:

1459208

Hom.:

148699

Cov.:

139

AF XY:

0.445

AC XY:

323023

AN XY:

725890

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.318

AC:

10507

AN:

33074

American (AMR)

AF:

0.581

AC:

25889

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10987

AN:

26112

East Asian (EAS)

AF:

0.705

AC:

27957

AN:

39650

South Asian (SAS)

AF:

0.425

AC:

36639

AN:

86170

European-Finnish (FIN)

AF:

0.490

AC:

26098

AN:

53240

Middle Eastern (MID)

AF:

0.432

AC:

2390

AN:

5536

European-Non Finnish (NFE)

AF:

0.436

AC:

484209

AN:

1110652

Other (OTH)

AF:

0.442

AC:

26623

AN:

60230

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.387

Heterozygous variant carriers

19523

39047

58570

78094

97617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14754

29508

44262

59016

73770

<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:

0.431

AC:

64807

AN:

150454

Hom.:

14462

Cov.:

AF XY:

0.438

AC XY:

32203

AN XY:

73478

show subpopulations

African (AFR)

AF:

0.329

AC:

13393

AN:

40690

American (AMR)

AF:

0.537

AC:

8121

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1500

AN:

3462

East Asian (EAS)

AF:

0.658

AC:

3327

AN:

5058

South Asian (SAS)

AF:

0.433

AC:

2044

AN:

4724

European-Finnish (FIN)

AF:

0.507

AC:

5297

AN:

10454

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29593

AN:

67658

Other (OTH)

AF:

0.449

AC:

929

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1603

3206

4809

6412

8015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.430

Hom.:

2421

Bravo

AF:

0.431

ExAC

AF:

0.454

AC:

54754

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

0.054

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.015

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0000067

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-1.6

PhyloP100

-5.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.020

REVEL

Benign

0.065

Sift

Benign

1.0

Vest4

0.041

ClinPred

0.0074

GERP RS

-6.2

Varity_R

0.019

gMVP

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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