11-1255545-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.16053C>T(p.Thr5351Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,479,462 control chromosomes in the GnomAD database, including 411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 64 hom., cov: 31)

Exomes 𝑓: 0.010 ( 347 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.21

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-1255545-C-T is Benign according to our data. Variant chr11-1255545-C-T is described in ClinVar as [Benign]. Clinvar id is 164006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0247 (3753/152028) while in subpopulation NFE AF= 0.0324 (2200/67924). AF 95% confidence interval is 0.0313. There are 64 homozygotes in gnomad4. There are 1861 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3753 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.16053C>T	p.Thr5351Thr	synonymous_variant	Exon 37 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.16053C>T	p.Thr5351Thr	synonymous_variant	Exon 37 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3754

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0324

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0126

AC:

1822

AN:

144344

Hom.:

AF XY:

0.0119

AC XY:

918

AN XY:

77120

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00659

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0103

AC:

13691

AN:

1327434

Hom.:

347

Cov.:

AF XY:

0.0105

AC XY:

6849

AN XY:

652996

show subpopulations

Gnomad4 AFR exome

AF:

0.00525

Gnomad4 AMR exome

AF:

0.00334

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00580

Gnomad4 FIN exome

AF:

0.0659

Gnomad4 NFE exome

AF:

0.00869

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.0247

AC:

3753

AN:

152028

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

1861

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0324

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00318

AC:

AN:

3476

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 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MUC5B: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Thr5351Thr in exon 37 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 2.6% (203/7862) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs117452757). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.55

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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