rs55856616

Positions:

chr11-1259008-G-A

Variant summary

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

The NM_002458.3(MUC5B):c.16660G>A(p.Asp5554Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,560,460 control chromosomes in the GnomAD database, including 1,401 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 (★★).

Frequency

Genomes: 𝑓 0.049 ( 237 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1164 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.46

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021681786).

BP6

Variant 11-1259008-G-A is Benign according to our data. Variant chr11-1259008-G-A is described in ClinVar as [Benign]. Clinvar id is 164011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16660G>A	p.Asp5554Asn	missense_variant	44/49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.16660G>A	p.Asp5554Asn	missense_variant	44/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000526859.1 linkuse as main transcript	c.295G>A	p.Asp99Asn	missense_variant	4/6	3		ENSP00000434539

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7372

AN:

152012

Hom.:

234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0327

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0658

Gnomad FIN

AF:

0.00839

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0321

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.0375

AC:

6415

AN:

171098

Hom.:

188

AF XY:

0.0396

AC XY:

3606

AN XY:

91012

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.0227

Gnomad ASJ exome

AF:

0.0877

Gnomad EAS exome

AF:

0.00324

Gnomad SAS exome

AF:

0.0701

Gnomad FIN exome

AF:

0.00928

Gnomad NFE exome

AF:

0.0307

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0359

AC:

50572

AN:

1408330

Hom.:

1164

Cov.:

AF XY:

0.0371

AC XY:

25795

AN XY:

695514

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.0250

Gnomad4 ASJ exome

AF:

0.0834

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.0705

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0324

Gnomad4 OTH exome

AF:

0.0421

GnomAD4 genome

AF:

0.0486

AC:

7390

AN:

152130

Hom.:

237

Cov.:

AF XY:

0.0472

AC XY:

3510

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0939

Gnomad4 AMR

AF:

0.0327

Gnomad4 ASJ

AF:

0.0764

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0650

Gnomad4 FIN

AF:

0.00839

Gnomad4 NFE

AF:

0.0321

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0375

Hom.:

155

Bravo

AF:

0.0520

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0327

AC:

126

ESP6500AA

AF:

0.0845

AC:

329

ESP6500EA

AF:

0.0301

AC:

247

ExAC

AF:

0.0239

AC:

2681

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Asp5554Asn in exon 44 of MUC5B: This variant is not expected to have clinical si gnificance because it has been identified in 8.4% (329/3894) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs55856616). -

MUC5B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 31, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

DANN

Benign

0.76

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.019

Sift

Benign

0.30

T;T

Sift4G

Benign

0.44

.;T

Vest4

0.015

ClinPred

0.0027

GERP RS

1.6

Varity_R

0.041

gMVP

0.89

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