rs3021163

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.9807T>C(p.Ser3269Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,438,560 control chromosomes in the GnomAD database, including 215,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20410 hom., cov: 27)

Exomes 𝑓: 0.50 ( 194884 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.75

Publications

13 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 11-1246687-T-C is Benign according to our data. Variant chr11-1246687-T-C is described in ClinVar as Benign. ClinVar VariationId is 403158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9807T>C	p.Ser3269Ser	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+2934A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9807T>C	p.Ser3269Ser	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+2934A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

76245

AN:

146484

Hom.:

20376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.540

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.529

GnomAD2 exomes

AF:

0.531

AC:

120411

AN:

226802

AF XY:

0.524

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.545

Gnomad NFE exome

AF:

0.488

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.504

AC:

650855

AN:

1291952

Hom.:

194884

Cov.:

107

AF XY:

0.503

AC XY:

325560

AN XY:

647240

show subpopulations

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

African (AFR)

AF:

0.496

AC:

14961

AN:

30176

American (AMR)

AF:

0.616

AC:

26940

AN:

43764

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

13076

AN:

24534

East Asian (EAS)

AF:

0.712

AC:

27586

AN:

38764

South Asian (SAS)

AF:

0.505

AC:

41398

AN:

81954

European-Finnish (FIN)

AF:

0.558

AC:

28487

AN:

51034

Middle Eastern (MID)

AF:

0.522

AC:

2793

AN:

5346

European-Non Finnish (NFE)

AF:

0.486

AC:

467833

AN:

961846

Other (OTH)

AF:

0.509

AC:

27781

AN:

54534

⚠️ 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: 0.343

Heterozygous variant carriers

19678

39355

59033

78710

98388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11956

23912

35868

47824

59780

<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:

0.521

AC:

76330

AN:

146608

Hom.:

20410

Cov.:

AF XY:

0.526

AC XY:

37584

AN XY:

71410

show subpopulations

African (AFR)

AF:

0.501

AC:

20160

AN:

40242

American (AMR)

AF:

0.586

AC:

8799

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

1818

AN:

3376

East Asian (EAS)

AF:

0.661

AC:

3246

AN:

4908

South Asian (SAS)

AF:

0.511

AC:

2379

AN:

4652

European-Finnish (FIN)

AF:

0.579

AC:

5639

AN:

9736

Middle Eastern (MID)

AF:

0.514

AC:

145

AN:

282

European-Non Finnish (NFE)

AF:

0.498

AC:

32555

AN:

65430

Other (OTH)

AF:

0.533

AC:

1097

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1591

3182

4773

6364

7955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.506

Hom.:

3732

Bravo

AF:

0.522

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

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.2

(source)

DANN

Benign

0.45

PhyloP100

-2.7

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