Genetic Variant MUC5B:p.Phe4916Phe (chr11-1251628-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_002458.3(MUC5B):c.14748C>T(p.Phe4916Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,612,710 control chromosomes in the GnomAD database, including 79,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6937 hom., cov: 33)

Exomes 𝑓: 0.31 ( 72823 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

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=-0.83).

BP6

Variant 11-1251628-C-T is Benign according to our data. Variant chr11-1251628-C-T is described in ClinVar as [Benign]. Clinvar id is 403180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.14748C>T	p.Phe4916Phe	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.14748C>T	p.Phe4916Phe	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44394

AN:

152092

Hom.:

6923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.320

AC:

79050

AN:

247284

Hom.:

13547

AF XY:

0.318

AC XY:

42759

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.611

Gnomad SAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.311

AC:

454507

AN:

1460500

Hom.:

72823

Cov.:

AF XY:

0.309

AC XY:

224794

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.595

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.292

AC:

44433

AN:

152210

Hom.:

6937

Cov.:

AF XY:

0.293

AC XY:

21816

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.599

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.304

Hom.:

11391

Bravo

AF:

0.293

Asia WGS

AF:

0.482

AC:

1673

AN:

3478

EpiCase

AF:

0.309

EpiControl

AF:

0.312

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.83

CADD

Benign

1.5

DANN

Benign

0.73

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