NM_002458.3:c.5822C>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.5822C>G(p.Thr1941Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,613,430 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 6 hom., cov: 32)

Exomes 𝑓: 0.030 ( 4 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.245

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 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=0.0031417608).

BP6

Variant 11-1242702-C-G is Benign according to our data. Variant chr11-1242702-C-G is described in ClinVar as Benign. ClinVar VariationId is 403132.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 = 0.0246 (3741/151826) while in subpopulation NFE AF = 0.0323 (2195/67856). AF 95% confidence interval is 0.0312. There are 6 homozygotes in GnomAd4. There are 1865 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.5822C>G	p.Thr1941Ser	missense	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.57-64G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.5822C>G	p.Thr1941Ser	missense	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-64G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3742

AN:

151708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00748

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00811

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0226

GnomAD2 exomes

AF:

0.0262

AC:

6524

AN:

249252

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0720

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0296

AC:

43274

AN:

1461604

Hom.:

Cov.:

107

AF XY:

0.0290

AC XY:

21078

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.0117

AC:

391

AN:

33478

American (AMR)

AF:

0.00568

AC:

254

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

755

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39688

South Asian (SAS)

AF:

0.00934

AC:

806

AN:

86256

European-Finnish (FIN)

AF:

0.0700

AC:

3738

AN:

53402

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0321

AC:

35677

AN:

1111808

Other (OTH)

AF:

0.0269

AC:

1624

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

3298

6597

9895

13194

16492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0246

AC:

3741

AN:

151826

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1865

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.0129

AC:

535

AN:

41392

American (AMR)

AF:

0.00747

AC:

114

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5136

South Asian (SAS)

AF:

0.00812

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.0673

AC:

714

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0323

AC:

2195

AN:

67856

Other (OTH)

AF:

0.0224

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0303

Hom.:

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.0131

AC:

ESP6500EA

AF:

0.0315

AC:

268

ExAC

AF:

0.0273

AC:

3306

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.031

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.24

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.67

REVEL

Benign

0.024

Sift

Benign

0.037

Vest4

0.027

ClinPred

0.00013

GERP RS

1.2

Varity_R

0.042

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over