Variant rs56229218 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.15972T>C(p.Leu5324=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,537,202 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 64 hom., cov: 31)

Exomes 𝑓: 0.011 ( 349 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.64

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=-0.95).

BP6

Variant 11-1255464-T-C is Benign according to our data. Variant chr11-1255464-T-C is described in ClinVar as [Benign]. Clinvar id is 178795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.64 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3774/151982) while in subpopulation NFE AF= 0.0325 (2206/67880). AF 95% confidence interval is 0.0314. There are 64 homozygotes in gnomad4. There are 1873 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.15972T>C	p.Leu5324=	synonymous_variant	37/49	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.15972T>C	p.Leu5324=	synonymous_variant	37/49	5	NM_002458.3	ENSP00000436812	P1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3775

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0689

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0124

AC:

2577

AN:

207460

Hom.:

AF XY:

0.0118

AC XY:

1334

AN XY:

113070

show subpopulations

Gnomad AFR exome

AF:

0.00979

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00668

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00284

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0147

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.0106

AC:

14721

AN:

1385220

Hom.:

349

Cov.:

AF XY:

0.0109

AC XY:

7504

AN XY:

688922

show subpopulations

Gnomad4 AFR exome

AF:

0.00538

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00570

Gnomad4 FIN exome

AF:

0.0653

Gnomad4 NFE exome

AF:

0.00907

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0248

AC:

3774

AN:

151982

Hom.:

Cov.:

AF XY:

0.0252

AC XY:

1873

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00746

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.0689

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0198

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

Leu5324Leu in exon 37 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 3.1% (256/8274) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56229218). -

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

-0.95

CADD

Benign

0.12

DANN

Benign

0.29

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