Variant 11-1255237-A-G 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.15861A>G(p.Pro5287Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,151,180 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 59 hom., cov: 18)

Exomes 𝑓: 0.037 ( 765 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -7.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP6

Variant 11-1255237-A-G is Benign according to our data. Variant chr11-1255237-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 178794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1255237-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-7.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 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.15861A>G	p.Pro5287Pro	synonymous_variant	36/49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.15861A>G	p.Pro5287Pro	synonymous_variant	36/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

3680

AN:

65764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.000449

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0237

AC:

3335

AN:

141004

Hom.:

AF XY:

0.0231

AC XY:

1728

AN XY:

74872

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.0274

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00916

Gnomad FIN exome

AF:

0.0712

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0369

AC:

40072

AN:

1085376

Hom.:

765

Cov.:

AF XY:

0.0361

AC XY:

19280

AN XY:

534404

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.00710

Gnomad4 ASJ exome

AF:

0.0424

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00992

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0390

Gnomad4 OTH exome

AF:

0.0361

GnomAD4 genome

AF:

0.0559

AC:

3679

AN:

65804

Hom.:

Cov.:

AF XY:

0.0582

AC XY:

1819

AN XY:

31268

show subpopulations

Gnomad4 AFR

AF:

0.0324

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0542

Gnomad4 EAS

AF:

0.000450

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.0624

Gnomad4 OTH

AF:

0.0548

Alfa

AF:

0.0299

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Pro5287Pro in exon 36 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 7.0% (13/186) of F innish chromosomes from a broad population by the 1000 Genomes Project (http://w ww.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs56344012). -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 03, 2014	- -

not provided

Benign:1

Likely 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

-1.0

CADD

Benign

0.0030

DANN

Benign

0.17

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