rs55845452

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002458.3(MUC5B):c.16110C>A(p.Pro5370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 734,482 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 31)

Exomes 𝑓: 0.028 ( 349 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-1256199-C-A is Benign according to our data. Variant chr11-1256199-C-A is described in ClinVar as [Benign]. Clinvar id is 178797.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3804/152218) while in subpopulation NFE AF= 0.0327 (2226/67980). AF 95% confidence interval is 0.0316. There are 63 homozygotes in gnomad4. There are 1894 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd at 3805 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16110C>A	p.Pro5370=	synonymous_variant	38/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.16110C>A	p.Pro5370=	synonymous_variant	38/49	5	NM_002458.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0256

AC:

4636

AN:

181320

Hom.:

AF XY:

0.0250

AC XY:

2422

AN XY:

96964

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00537

Gnomad ASJ exome

AF:

0.0279

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00969

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0263

GnomAD4 exome

AF:

0.0278

AC:

16159

AN:

582264

Hom.:

349

Cov.:

AF XY:

0.0264

AC XY:

8332

AN XY:

315182

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.0281

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00972

Gnomad4 FIN exome

AF:

0.0722

Gnomad4 NFE exome

AF:

0.0312

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.0250

AC:

3804

AN:

152218

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1894

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0295

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Pro5370Pro in exon 38 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 2.8% (234/8374) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs55845452). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.028

Dann

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over