11-1258382-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.16593+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,611,084 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 61 hom., cov: 32)

Exomes 𝑓: 0.030 ( 831 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.31

Publications

3 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 Gene-Disease associations (from GenCC):

interstitial lung disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MUC5B 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 (BayesDel_noAF=-0.92).

BP6

Variant 11-1258382-G-C is Benign according to our data. Variant chr11-1258382-G-C is described in ClinVar as Benign. ClinVar VariationId is 226736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.025 (3802/152304) while in subpopulation NFE AF = 0.0327 (2227/68008). AF 95% confidence interval is 0.0316. There are 61 homozygotes in GnomAd4. There are 1887 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.16593+15G>C		intron_variant	Intron 43 of 48	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.16593+15G>C		intron_variant	Intron 43 of 48	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000526859.1 link	c.228+15G>C		intron_variant	Intron 3 of 5	3		ENSP00000434539.1		H0YDX8

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3803

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0260

AC:

6379

AN:

245256

AF XY:

0.0256

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0728

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0300

AC:

43718

AN:

1458780

Hom.:

831

Cov.:

AF XY:

0.0293

AC XY:

21262

AN XY:

725560

show subpopulations

African (AFR)

AF:

0.0118

AC:

394

AN:

33464

American (AMR)

AF:

0.00547

AC:

244

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.0290

AC:

755

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00944

AC:

812

AN:

86010

European-Finnish (FIN)

AF:

0.0722

AC:

3750

AN:

51956

Middle Eastern (MID)

AF:

0.00469

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0325

AC:

36090

AN:

1110956

Other (OTH)

AF:

0.0273

AC:

1646

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

2152

4304

6456

8608

10760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1326

2652

3978

5304

6630

<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:

0.0250

AC:

3802

AN:

152304

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

1887

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0131

AC:

543

AN:

41566

American (AMR)

AF:

0.00745

AC:

114

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00807

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0688

AC:

731

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0327

AC:

2227

AN:

68008

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

197

394

592

789

986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0308

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.16593+15G>C in 43 of MUC5B: This variant is not expected to have clinical sign ificance because it has been identified in 4% (2330/62894) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs56025628). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.33

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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