rs60268710

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.9452C>T(p.Thr3151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,516 control chromosomes in the GnomAD database, including 81,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6846 hom., cov: 31)

Exomes 𝑓: 0.31 ( 74306 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.736798E-5).

BP6

Variant 11-1246332-C-T is Benign according to our data. Variant chr11-1246332-C-T is described in ClinVar as [Benign]. Clinvar id is 403151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9452C>T	p.Thr3151Met	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+3289G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9452C>T	p.Thr3151Met	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+3289G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44102

AN:

151132

Hom.:

6832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.322

AC:

80076

AN:

248712

Hom.:

13939

AF XY:

0.320

AC XY:

43233

AN XY:

134998

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.313

AC:

457578

AN:

1461266

Hom.:

74306

Cov.:

122

AF XY:

0.312

AC XY:

226464

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.292

AC:

44136

AN:

151250

Hom.:

6846

Cov.:

AF XY:

0.293

AC XY:

21643

AN XY:

73870

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.592

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.300

Hom.:

2207

Bravo

AF:

0.294

ESP6500AA

AF:

0.192

AC:

782

ESP6500EA

AF:

0.298

AC:

2471

ExAC

AF:

0.320

AC:

38643

EpiCase

AF:

0.310

EpiControl

AF:

0.313

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.9

DANN

Benign

0.71

DEOGEN2

Benign

0.021

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.68

MetaRNN

Benign

0.000037

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

REVEL

Benign

0.044

Sift

Uncertain

0.026

Vest4

0.032

ClinPred

0.0053

GERP RS

-3.5

Varity_R

0.019

gMVP

0.27

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