Variant rs145066684 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002458.3(MUC5B):c.14718T>C(p.Pro4906=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,612,970 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.021 ( 50 hom., cov: 33)

Exomes 𝑓: 0.028 ( 732 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.85

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-1251598-T-C is Benign according to our data. Variant chr11-1251598-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403198.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-7.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3224/152332) while in subpopulation NFE AF= 0.0299 (2033/68018). AF 95% confidence interval is 0.0288. There are 50 homozygotes in gnomad4. There are 1626 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.14718T>C	p.Pro4906=	synonymous_variant	31/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.14718T>C	p.Pro4906=	synonymous_variant	31/49	5	NM_002458.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3223

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0240

AC:

5940

AN:

247506

Hom.:

124

AF XY:

0.0241

AC XY:

3250

AN XY:

134728

show subpopulations

Gnomad AFR exome

AF:

0.00574

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00926

Gnomad FIN exome

AF:

0.0737

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0276

AC:

40301

AN:

1460638

Hom.:

732

Cov.:

AF XY:

0.0270

AC XY:

19632

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.00341

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00936

Gnomad4 FIN exome

AF:

0.0715

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0212

AC:

3224

AN:

152332

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1626

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00500

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.0684

Gnomad4 NFE

AF:

0.0299

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0259

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0247

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely 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

0.30

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