Variant rs11605113 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002458.3(MUC5B):c.6252A>G(p.Thr2084Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,606,930 control chromosomes in the GnomAD database, including 80,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6796 hom., cov: 27)

Exomes 𝑓: 0.31 ( 74033 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.70

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:):

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=-1.02).

BP6

Variant 11-1243132-A-G is Benign according to our data. Variant chr11-1243132-A-G is described in ClinVar as [Benign]. Clinvar id is 403135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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.6252A>G	p.Thr2084Thr	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.57-494T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.6252A>G	p.Thr2084Thr	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.57-494T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

43564

AN:

149072

Hom.:

6784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.327

AC:

79208

AN:

242464

Hom.:

14410

AF XY:

0.325

AC XY:

42843

AN XY:

131812

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.313

AC:

456536

AN:

1457736

Hom.:

74033

Cov.:

116

AF XY:

0.312

AC XY:

225913

AN XY:

725118

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.292

AC:

43597

AN:

149194

Hom.:

6796

Cov.:

AF XY:

0.293

AC XY:

21341

AN XY:

72726

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.294

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.279

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.294

Hom.:

1173

Bravo

AF:

0.295

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

-1.0

CADD

Benign

2.2

DANN

Benign

0.36

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