rs2672810

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.1287C>T(p.Gly429Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,972 control chromosomes in the GnomAD database, including 897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 57 hom., cov: 34)

Exomes 𝑓: 0.030 ( 840 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.80

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 11-1230071-C-T is Benign according to our data. Variant chr11-1230071-C-T is described in ClinVar as Benign. ClinVar VariationId is 178788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3479/152278) while in subpopulation NFE AF = 0.0328 (2227/67990). AF 95% confidence interval is 0.0316. There are 57 homozygotes in GnomAd4. There are 1735 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.1345C>T		non_coding_transcript_exon_variant	Exon 11 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3479

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00555

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0260

AC:

6441

AN:

247508

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.00642

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0278

GnomAD4 exome

AF:

0.0300

AC:

43718

AN:

1459694

Hom.:

840

Cov.:

AF XY:

0.0293

AC XY:

21294

AN XY:

726134

show subpopulations

African (AFR)

AF:

0.00388

AC:

130

AN:

33466

American (AMR)

AF:

0.00527

AC:

235

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

761

AN:

26080

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00951

AC:

819

AN:

86148

European-Finnish (FIN)

AF:

0.0729

AC:

3800

AN:

52144

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0327

AC:

36314

AN:

1111470

Other (OTH)

AF:

0.0270

AC:

1631

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

2462

4924

7387

9849

12311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1330

2660

3990

5320

6650

<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:

0.0228

AC:

3479

AN:

152278

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1735

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00553

AC:

230

AN:

41570

American (AMR)

AF:

0.00673

AC:

103

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00808

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0694

AC:

737

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0328

AC:

2227

AN:

67990

Other (OTH)

AF:

0.0199

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

180

360

540

720

900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0285

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0252

EpiControl

AF:

0.0264

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

Gly429Gly in exon 11 of MUC5B: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 3.3% (271/8284) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2672810). -

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

-0.75

CADD

Benign

0.44

(source)

DANN

Benign

0.56

PhyloP100

-5.8

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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