Variant 11-1245466-A-C 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.8586A>C(p.Pro2862Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,095,550 control chromosomes in the GnomAD database, including 77,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 2950 hom., cov: 17)

Exomes 𝑓: 0.18 ( 77194 hom. )

Failed GnomAD Quality Control

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.58

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=-1.06).

BP6

Variant 11-1245466-A-C is Benign according to our data. Variant chr11-1245466-A-C is described in ClinVar as [Benign]. Clinvar id is 403147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.58 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 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.8586A>C	p.Pro2862Pro	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.57-2828T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.8586A>C	p.Pro2862Pro	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.57-2828T>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

14723

AN:

73454

Hom.:

2947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.266

AC:

44800

AN:

168454

Hom.:

18807

AF XY:

0.260

AC XY:

23920

AN XY:

91972

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.575

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.178

AC:

194919

AN:

1095550

Hom.:

77194

Cov.:

AF XY:

0.184

AC XY:

100334

AN XY:

543980

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.200

AC:

14737

AN:

73506

Hom.:

2950

Cov.:

AF XY:

0.193

AC XY:

6796

AN XY:

35228

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.224

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.389

Hom.:

2638

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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-1.1

CADD

Benign

2.1

DANN

Benign

0.60

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