11-1243132-A-G

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.6252A>G(p.Thr2084Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,606,930 control chromosomes in the GnomAD database, including 80,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6796 hom., cov: 27)

Exomes 𝑓: 0.31 ( 74033 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.70

Publications

8 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=-1.02).

BP6

Variant 11-1243132-A-G is Benign according to our data. Variant chr11-1243132-A-G is described in ClinVar as Benign. ClinVar VariationId is 403135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.6252A>G	p.Thr2084Thr	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-494T>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.6252A>G	p.Thr2084Thr	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-494T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

43564

AN:

149072

Hom.:

6784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.327

AC:

79208

AN:

242464

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.609

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.313

AC:

456536

AN:

1457736

Hom.:

74033

Cov.:

116

AF XY:

0.312

AC XY:

225913

AN XY:

725118

show subpopulations

African (AFR)

AF:

0.212

AC:

7085

AN:

33420

American (AMR)

AF:

0.307

AC:

13698

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7577

AN:

26090

East Asian (EAS)

AF:

0.601

AC:

23837

AN:

39684

South Asian (SAS)

AF:

0.280

AC:

24168

AN:

86166

European-Finnish (FIN)

AF:

0.285

AC:

15143

AN:

53114

Middle Eastern (MID)

AF:

0.278

AC:

1346

AN:

4836

European-Non Finnish (NFE)

AF:

0.311

AC:

344733

AN:

1109644

Other (OTH)

AF:

0.315

AC:

18949

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

22829

45658

68488

91317

114146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11342

22684

34026

45368

56710

<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:

0.292

AC:

43597

AN:

149194

Hom.:

6796

Cov.:

AF XY:

0.293

AC XY:

21341

AN XY:

72726

show subpopulations

African (AFR)

AF:

0.217

AC:

8801

AN:

40624

American (AMR)

AF:

0.331

AC:

4975

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1009

AN:

3428

East Asian (EAS)

AF:

0.591

AC:

2885

AN:

4882

South Asian (SAS)

AF:

0.287

AC:

1348

AN:

4694

European-Finnish (FIN)

AF:

0.279

AC:

2831

AN:

10164

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.308

AC:

20689

AN:

67092

Other (OTH)

AF:

0.319

AC:

660

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1294

2588

3883

5177

6471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.294

Hom.:

1173

Bravo

AF:

0.295

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

(source)

DANN

Benign

0.36

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