rs34739266

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.6073G>A(p.Ala2025Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,611,204 control chromosomes in the GnomAD database, including 16,603 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 0.11 ( 1023 hom., cov: 31)

Exomes 𝑓: 0.14 ( 15580 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.36

Publications

14 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=0.0015899241).

BP6

Variant 11-1242953-G-A is Benign according to our data. Variant chr11-1242953-G-A is described in ClinVar as Benign. ClinVar VariationId is 403133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.6073G>A	p.Ala2025Thr	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 link	n.57-315C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.6073G>A	p.Ala2025Thr	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2 link	n.57-315C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16143

AN:

149706

Hom.:

1020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.0908

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0873

Gnomad MID

AF:

0.176

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.120

AC:

29870

AN:

249148

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.0932

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.142

AC:

207502

AN:

1461380

Hom.:

15580

Cov.:

139

AF XY:

0.143

AC XY:

103927

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.0496

AC:

1661

AN:

33476

American (AMR)

AF:

0.0667

AC:

2983

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

4946

AN:

26134

East Asian (EAS)

AF:

0.0217

AC:

862

AN:

39696

South Asian (SAS)

AF:

0.154

AC:

13241

AN:

86232

European-Finnish (FIN)

AF:

0.0978

AC:

5221

AN:

53366

Middle Eastern (MID)

AF:

0.161

AC:

927

AN:

5768

European-Non Finnish (NFE)

AF:

0.153

AC:

169531

AN:

1111646

Other (OTH)

AF:

0.135

AC:

8130

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

12106

24211

36317

48422

60528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5900

11800

17700

23600

29500

<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:

0.108

AC:

16145

AN:

149824

Hom.:

1023

Cov.:

AF XY:

0.105

AC XY:

7652

AN XY:

73094

show subpopulations

African (AFR)

AF:

0.0485

AC:

1968

AN:

40544

American (AMR)

AF:

0.0906

AC:

1370

AN:

15114

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

602

AN:

3460

East Asian (EAS)

AF:

0.0185

AC:

AN:

5026

South Asian (SAS)

AF:

0.150

AC:

707

AN:

4708

European-Finnish (FIN)

AF:

0.0873

AC:

898

AN:

10288

Middle Eastern (MID)

AF:

0.177

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.150

AC:

10101

AN:

67420

Other (OTH)

AF:

0.110

AC:

228

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

710

1420

2130

2840

3550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.143

Hom.:

545

Bravo

AF:

0.105

ESP6500AA

AF:

0.0446

AC:

188

ESP6500EA

AF:

0.150

AC:

1261

ExAC

AF:

0.122

AC:

14797

EpiCase

AF:

0.160

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.048

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.015

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

PhyloP100

-2.4

PrimateAI

Benign

0.21

PROVEAN

Benign

0.35

REVEL

Benign

0.037

Sift

Benign

1.0

Vest4

0.015

ClinPred

0.000020

GERP RS

-1.7

Varity_R

0.018

gMVP

0.13

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

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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