rs377351415

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002458.3(MUC5B):c.1497C>T(p.Gly499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,596,910 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 2 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.18

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-1230962-C-T is Benign according to our data. Variant chr11-1230962-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BS2

High AC in GnomAd at 214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.1497C>T	p.Gly499=	synonymous_variant	13/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.1497C>T	p.Gly499=	synonymous_variant	13/49	5	NM_002458.3	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.1555C>T		non_coding_transcript_exon_variant	13/26	1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00135

AC:

296

AN:

220052

Hom.:

AF XY:

0.00140

AC XY:

168

AN XY:

120144

show subpopulations

Gnomad AFR exome

AF:

0.000242

Gnomad AMR exome

AF:

0.000772

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000553

Gnomad FIN exome

AF:

0.000586

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.00223

AC:

3224

AN:

1444776

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1582

AN XY:

717276

show subpopulations

Gnomad4 AFR exome

AF:

0.000423

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000650

Gnomad4 FIN exome

AF:

0.000555

Gnomad4 NFE exome

AF:

0.00270

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152134

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	MUC5B: BP4, BP7 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

p.Gly499Gly in exon 13 of MUC5B: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.25% (276/111590 ) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gno mad.broadinstitute.org; dbSNP rs377351415). ACMG/AMP Criteria applied: BP4, BP7. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

1.6

Dann

Benign

0.85

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