rs12286473

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.6780A>G(p.Arg2260Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,576,616 control chromosomes in the GnomAD database, including 24,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1442 hom., cov: 29)

Exomes 𝑓: 0.16 ( 22828 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.09).

BP6

Variant 11-1243660-A-G is Benign according to our data. Variant chr11-1243660-A-G is described in ClinVar as [Benign]. Clinvar id is 403141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.6780A>G	p.Arg2260Arg	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-1022T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.6780A>G	p.Arg2260Arg	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-1022T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18649

AN:

149074

Hom.:

1441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0533

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.0949

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0180

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.129

AC:

30996

AN:

240444

Hom.:

3070

AF XY:

0.134

AC XY:

17445

AN XY:

130284

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.0622

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0159

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.164

AC:

234461

AN:

1427426

Hom.:

22828

Cov.:

170

AF XY:

0.165

AC XY:

117322

AN XY:

710972

show subpopulations

Gnomad4 AFR exome

AF:

0.0538

Gnomad4 AMR exome

AF:

0.0707

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.0219

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.125

AC:

18637

AN:

149190

Hom.:

1442

Cov.:

AF XY:

0.121

AC XY:

8836

AN XY:

72786

show subpopulations

Gnomad4 AFR

AF:

0.0530

Gnomad4 AMR

AF:

0.0947

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.0181

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.164

Hom.:

979

Bravo

AF:

0.122

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

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.9

DANN

Benign

0.15

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