Variant rs2037089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.4797T>C(p.Ser1599Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,611,266 control chromosomes in the GnomAD database, including 34,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4130 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30789 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.46

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-1241677-T-C is Benign according to our data. Variant chr11-1241677-T-C is described in ClinVar as [Benign]. Clinvar id is 196682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.4797T>C	p.Ser1599Ser	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.4797T>C	p.Ser1599Ser	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34593

AN:

151736

Hom.:

4112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.220

AC:

53472

AN:

242542

Hom.:

6429

AF XY:

0.216

AC XY:

28604

AN XY:

132400

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.0600

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.201

AC:

293564

AN:

1459412

Hom.:

30789

Cov.:

AF XY:

0.202

AC XY:

146509

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.228

AC:

34641

AN:

151854

Hom.:

4130

Cov.:

AF XY:

0.233

AC XY:

17259

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.0693

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.210

Hom.:

1736

Bravo

AF:

0.228

Asia WGS

AF:

0.136

AC:

475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 22, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.67

DANN

Benign

0.53

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