Genetic Variant MUC5B:p.Pro3866Arg (chr11-1248477-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002458.3(MUC5B):c.11597C>G(p.Pro3866Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3866L) has been classified as Benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.43

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07300487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.11597C>G	p.Pro3866Arg	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+1144G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.11597C>G	p.Pro3866Arg	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+1144G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243446

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453886

Hom.:

Cov.:

153

AF XY:

0.00000138

AC XY:

AN XY:

723448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105768

Other (OTH)

AF:

0.00

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.018

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.033

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.17

M_CAP

Benign

0.0014

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-4.4

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.025

Sift

Benign

0.12

Vest4

0.060

MVP

0.043

ClinPred

0.037

GERP RS

0.12

Varity_R

0.036

gMVP

0.39

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over