rs80150964

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_002458.3(MUC5B):c.8606T>C(p.Met2869Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1062 hom., cov: 18)

Exomes 𝑓: 0.10 ( 32064 hom. )

Failed GnomAD Quality Control

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.43

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051601827).

BP6

Variant 11-1245486-T-C is Benign according to our data. Variant chr11-1245486-T-C is described in ClinVar as [Benign]. Clinvar id is 403148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.8606T>C	p.Met2869Thr	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-2848A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.8606T>C	p.Met2869Thr	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-2848A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

8502

AN:

79860

Hom.:

1063

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.0584

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0823

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0974

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.207

AC:

35062

AN:

169532

Hom.:

12373

AF XY:

0.205

AC XY:

19000

AN XY:

92670

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.526

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.104

AC:

113079

AN:

1084454

Hom.:

32064

Cov.:

AF XY:

0.108

AC XY:

57985

AN XY:

538972

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.106

AC:

8498

AN:

79882

Hom.:

1062

Cov.:

AF XY:

0.101

AC XY:

3871

AN XY:

38456

show subpopulations

Gnomad4 AFR

AF:

0.0994

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0823

Gnomad4 NFE

AF:

0.0974

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.290

Hom.:

1465

ExAC

AF:

0.247

AC:

28544

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 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.036

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.096

DANN

Benign

0.54

DEOGEN2

Benign

0.015

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00042

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.34

PROVEAN

Benign

1.0

REVEL

Benign

0.038

Sift

Benign

1.0

Vest4

0.0060

ClinPred

0.0013

GERP RS

-1.7

Varity_R

0.029

gMVP

0.75

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