Variant chr11-1254363-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002458.3(MUC5B):c.15477+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,598,332 control chromosomes in the GnomAD database, including 1,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 231 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1211 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.04

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 (BayesDel_noAF=-0.89).

BP6

Variant 11-1254363-C-A is Benign according to our data. Variant chr11-1254363-C-A is described in ClinVar as [Benign]. Clinvar id is 178793.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.15477+12C>A		intron_variant		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.15477+12C>A		intron_variant		5	NM_002458.3	ENSP00000436812	P1

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7376

AN:

152174

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0649

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0321

Gnomad OTH

AF:

0.0465

GnomAD3 exomes

AF:

0.0387

AC:

9107

AN:

235250

Hom.:

260

AF XY:

0.0403

AC XY:

5205

AN XY:

129270

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0874

Gnomad EAS exome

AF:

0.00370

Gnomad SAS exome

AF:

0.0714

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.0309

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0361

AC:

52202

AN:

1446040

Hom.:

1211

Cov.:

AF XY:

0.0373

AC XY:

26851

AN XY:

719528

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.0237

Gnomad4 ASJ exome

AF:

0.0832

Gnomad4 EAS exome

AF:

0.00227

Gnomad4 SAS exome

AF:

0.0707

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0324

Gnomad4 OTH exome

AF:

0.0418

GnomAD4 genome

AF:

0.0486

AC:

7394

AN:

152292

Hom.:

231

Cov.:

AF XY:

0.0472

AC XY:

3518

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0938

Gnomad4 AMR

AF:

0.0327

Gnomad4 ASJ

AF:

0.0761

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0641

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.0321

Gnomad4 OTH

AF:

0.0451

Alfa

AF:

0.0451

Hom.:

Bravo

AF:

0.0521

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

15477+12C>A in intron 34 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 9.0% (378/4210) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs56352092). -

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.49

DANN

Benign

0.27

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