NM_002458.3:c.2631-9C>G

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.2631-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,607,038 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: 33)

Exomes 𝑓: 0.030 ( 831 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Splicing: ADA: 0.0002992

Clinical Significance

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

Conservation

PhyloP100: -0.342

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=-0.87).

BP6

Variant 11-1235076-C-G is Benign according to our data. Variant chr11-1235076-C-G is described in ClinVar as Benign. ClinVar VariationId is 178790.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 = 0.0251 (3827/152286) while in subpopulation NFE AF = 0.0327 (2222/67986). AF 95% confidence interval is 0.0316. There are 61 homozygotes in GnomAd4. There are 1911 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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.2631-9C>G		intron_variant	Intron 21 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.2631-9C>G		intron_variant	Intron 21 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5 link	n.2689-9C>G		intron_variant	Intron 21 of 25	1

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3828

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.0693

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0261

AC:

6337

AN:

242402

AF XY:

0.0260

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.00506

Gnomad ASJ exome

AF:

0.0278

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0733

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0301

AC:

43768

AN:

1454752

Hom.:

831

Cov.:

AF XY:

0.0294

AC XY:

21286

AN XY:

723140

show subpopulations

African (AFR)

AF:

0.0121

AC:

404

AN:

33438

American (AMR)

AF:

0.00571

AC:

253

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

745

AN:

25780

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00954

AC:

817

AN:

85678

European-Finnish (FIN)

AF:

0.0722

AC:

3722

AN:

51574

Middle Eastern (MID)

AF:

0.00458

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.0326

AC:

36151

AN:

1108620

Other (OTH)

AF:

0.0275

AC:

1650

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2276

4553

6829

9106

11382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1334

2668

4002

5336

6670

<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:

0.0251

AC:

3827

AN:

152286

Hom.:

Cov.:

AF XY:

0.0257

AC XY:

1911

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0136

AC:

566

AN:

41556

American (AMR)

AF:

0.00758

AC:

116

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00807

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0693

AC:

736

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0327

AC:

2222

AN:

67986

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

211

422

633

844

1055

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:

0.0293

Hom.:

Bravo

AF:

0.0200

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

2631-9C>G in intron 21 of MUC5B: This variant is not expected to have clinical s ignificance because it has been identified in 3.2% (265/8382) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs55771636). -

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

-0.87

CADD

Benign

4.3

(source)

DANN

Benign

0.49

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00030

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.080

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