11-1242293-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.5413G>A(p.Gly1805Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,613,860 control chromosomes in the GnomAD database, including 5,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 428 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4673 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.378

Publications

28 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024515688).

BP6

Variant 11-1242293-G-A is Benign according to our data. Variant chr11-1242293-G-A is described in ClinVar as [Benign]. Clinvar id is 1249409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.5413G>A	p.Gly1805Ser	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.402C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.5413G>A	p.Gly1805Ser	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.402C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10171

AN:

152118

Hom.:

428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.0572

Gnomad SAS

AF:

0.0916

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0743

Gnomad OTH

AF:

0.0712

GnomAD2 exomes

AF:

0.0845

AC:

21067

AN:

249244

AF XY:

0.0848

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0885

Gnomad EAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.0847

GnomAD4 exome

AF:

0.0761

AC:

111197

AN:

1461624

Hom.:

4673

Cov.:

AF XY:

0.0771

AC XY:

56059

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.0208

AC:

698

AN:

33480

American (AMR)

AF:

0.128

AC:

5719

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0920

AC:

2405

AN:

26136

East Asian (EAS)

AF:

0.102

AC:

4052

AN:

39700

South Asian (SAS)

AF:

0.0930

AC:

8025

AN:

86258

European-Finnish (FIN)

AF:

0.126

AC:

6697

AN:

53330

Middle Eastern (MID)

AF:

0.105

AC:

607

AN:

5768

European-Non Finnish (NFE)

AF:

0.0707

AC:

78595

AN:

1111856

Other (OTH)

AF:

0.0729

AC:

4399

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7975

15949

23924

31898

39873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0668

AC:

10165

AN:

152236

Hom.:

428

Cov.:

AF XY:

0.0707

AC XY:

5259

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0225

AC:

933

AN:

41548

American (AMR)

AF:

0.0930

AC:

1423

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0997

AC:

346

AN:

3472

East Asian (EAS)

AF:

0.0574

AC:

297

AN:

5178

South Asian (SAS)

AF:

0.0919

AC:

443

AN:

4822

European-Finnish (FIN)

AF:

0.132

AC:

1400

AN:

10600

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0743

AC:

5054

AN:

68004

Other (OTH)

AF:

0.0700

AC:

148

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

485

969

1454

1938

2423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0741

Hom.:

1429

Bravo

AF:

0.0625

TwinsUK

AF:

0.0739

AC:

274

ALSPAC

AF:

0.0732

AC:

282

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.0716

AC:

596

ExAC

AF:

0.0800

AC:

9674

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

EpiCase

AF:

0.0786

EpiControl

AF:

0.0770

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.021

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.38

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.055

Sift

Benign

0.18

Vest4

0.046

ClinPred

0.032

GERP RS

1.1

Varity_R

0.13

gMVP

0.87

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-1242293-G-A

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