rs2943527

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.10498A>G(p.Ser3500Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,554,524 control chromosomes in the GnomAD database, including 380,150 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 0.68 ( 34671 hom., cov: 25)

Exomes 𝑓: 0.69 ( 345479 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

Publications

18 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=1.4510267E-6).

BP6

Variant 11-1247378-A-G is Benign according to our data. Variant chr11-1247378-A-G is described in ClinVar as Benign. ClinVar VariationId is 403162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.10498A>G	p.Ser3500Gly	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+2243T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.10498A>G	p.Ser3500Gly	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+2243T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

100556

AN:

147734

Hom.:

34644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.676

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.683

GnomAD2 exomes

AF:

0.687

AC:

161050

AN:

234520

AF XY:

0.686

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.698

Gnomad EAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.767

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.692

AC:

972849

AN:

1406674

Hom.:

345479

Cov.:

115

AF XY:

0.690

AC XY:

483352

AN XY:

700224

show subpopulations

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

African (AFR)

AF:

0.647

AC:

20945

AN:

32388

American (AMR)

AF:

0.705

AC:

31042

AN:

44060

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

17593

AN:

25400

East Asian (EAS)

AF:

0.710

AC:

28121

AN:

39608

South Asian (SAS)

AF:

0.657

AC:

55633

AN:

84650

European-Finnish (FIN)

AF:

0.775

AC:

40023

AN:

51652

Middle Eastern (MID)

AF:

0.689

AC:

2769

AN:

4020

European-Non Finnish (NFE)

AF:

0.691

AC:

736608

AN:

1066620

Other (OTH)

AF:

0.688

AC:

40115

AN:

58276

⚠️ 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: 0.370

Heterozygous variant carriers

12975

25949

38924

51898

64873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18332

36664

54996

73328

91660

<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:

0.681

AC:

100634

AN:

147850

Hom.:

34671

Cov.:

AF XY:

0.685

AC XY:

49344

AN XY:

72034

show subpopulations

African (AFR)

AF:

0.644

AC:

25951

AN:

40298

American (AMR)

AF:

0.708

AC:

10669

AN:

15060

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2314

AN:

3364

East Asian (EAS)

AF:

0.664

AC:

3310

AN:

4982

South Asian (SAS)

AF:

0.641

AC:

2930

AN:

4572

European-Finnish (FIN)

AF:

0.790

AC:

7936

AN:

10050

Middle Eastern (MID)

AF:

0.666

AC:

193

AN:

290

European-Non Finnish (NFE)

AF:

0.683

AC:

45275

AN:

66294

Other (OTH)

AF:

0.688

AC:

1402

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1318

2637

3955

5274

6592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.670

Hom.:

6118

Bravo

AF:

0.673

ESP6500AA

AF:

0.489

AC:

2003

ESP6500EA

AF:

0.575

AC:

4798

ExAC

AF:

0.665

AC:

80346

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

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

0.050

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.27

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.017

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0000015

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.0

PhyloP100

-1.3

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.080

REVEL

Benign

0.010

Sift

Benign

0.30

Vest4

0.010

ClinPred

0.0030

GERP RS

-4.6

Varity_R

0.031

gMVP

0.25

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