11-1242546-C-T

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.5666C>T(p.Pro1889Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,674 control chromosomes in the GnomAD database, including 15,607 homozygotes. 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1528 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14079 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0850

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=0.0060792863).

BP6

Variant 11-1242546-C-T is Benign according to our data. Variant chr11-1242546-C-T is described in ClinVar as [Benign]. Clinvar id is 403131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.5666C>T	p.Pro1889Leu	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.149G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.5666C>T	p.Pro1889Leu	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.149G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20495

AN:

151938

Hom.:

1525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0595

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.151

AC:

37674

AN:

249322

Hom.:

3592

AF XY:

0.146

AC XY:

19787

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0507

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.133

AC:

194389

AN:

1461618

Hom.:

14079

Cov.:

AF XY:

0.133

AC XY:

96952

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.208

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.135

AC:

20509

AN:

152056

Hom.:

1528

Cov.:

AF XY:

0.141

AC XY:

10518

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.129

Hom.:

2349

Bravo

AF:

0.133

TwinsUK

AF:

0.131

AC:

484

ALSPAC

AF:

0.125

AC:

481

ESP6500AA

AF:

0.0962

AC:

421

ESP6500EA

AF:

0.125

AC:

1067

ExAC

AF:

0.142

AC:

17153

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

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

0.084

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.020

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.64

REVEL

Benign

0.059

Sift

Benign

0.12

Vest4

0.030

ClinPred

0.0015

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.025

gMVP

0.46

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