rs12286473

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.6780A>G(p.Arg2260Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,576,616 control chromosomes in the GnomAD database, including 24,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1442 hom., cov: 29)

Exomes 𝑓: 0.16 ( 22828 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

Publications

6 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=-1.09).

BP6

Variant 11-1243660-A-G is Benign according to our data. Variant chr11-1243660-A-G is described in ClinVar as Benign. ClinVar VariationId is 403141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.6780A>G	p.Arg2260Arg	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 link	n.57-1022T>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.6780A>G	p.Arg2260Arg	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2 link	n.57-1022T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18649

AN:

149074

Hom.:

1441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0533

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.0949

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0180

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.129

AC:

30996

AN:

240444

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.0622

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.164

AC:

234461

AN:

1427426

Hom.:

22828

Cov.:

170

AF XY:

0.165

AC XY:

117322

AN XY:

710972

show subpopulations

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

African (AFR)

AF:

0.0538

AC:

1787

AN:

33210

American (AMR)

AF:

0.0707

AC:

3151

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5549

AN:

25814

East Asian (EAS)

AF:

0.0219

AC:

871

AN:

39686

South Asian (SAS)

AF:

0.161

AC:

13860

AN:

85854

European-Finnish (FIN)

AF:

0.160

AC:

8321

AN:

51918

Middle Eastern (MID)

AF:

0.154

AC:

642

AN:

4174

European-Non Finnish (NFE)

AF:

0.176

AC:

191061

AN:

1083036

Other (OTH)

AF:

0.156

AC:

9219

AN:

59172

⚠️ 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: 0.389

Heterozygous variant carriers

10219

20438

30658

40877

51096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6290

12580

18870

25160

31450

<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:

0.125

AC:

18637

AN:

149190

Hom.:

1442

Cov.:

AF XY:

0.121

AC XY:

8836

AN XY:

72786

show subpopulations

African (AFR)

AF:

0.0530

AC:

2160

AN:

40724

American (AMR)

AF:

0.0947

AC:

1435

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

672

AN:

3416

East Asian (EAS)

AF:

0.0181

AC:

AN:

5086

South Asian (SAS)

AF:

0.151

AC:

705

AN:

4662

European-Finnish (FIN)

AF:

0.139

AC:

1422

AN:

10216

Middle Eastern (MID)

AF:

0.168

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.176

AC:

11715

AN:

66676

Other (OTH)

AF:

0.125

AC:

258

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

613

1226

1838

2451

3064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.164

Hom.:

979

Bravo

AF:

0.122

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-1.1

CADD

Benign

1.9

(source)

DANN

Benign

0.15

PhyloP100

-1.5

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