rs56141203

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002458.3(MUC5B):c.15478-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,607,834 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 63 hom., cov: 33)

Exomes 𝑓: 0.030 ( 832 hom. )

Consequence

MUC5B
NM_002458.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-1254681-T-C is Benign according to our data. Variant chr11-1254681-T-C is described in ClinVar as [Benign]. Clinvar id is 164003.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-1254681-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3807/152314) while in subpopulation NFE AF= 0.0328 (2228/68014). AF 95% confidence interval is 0.0316. There are 63 homozygotes in gnomad4. There are 1892 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 3808 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.15478-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.15478-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_002458.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3808

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0266

AC:

6521

AN:

245246

Hom.:

135

AF XY:

0.0265

AC XY:

3535

AN XY:

133616

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00942

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0301

AC:

43781

AN:

1455520

Hom.:

832

Cov.:

AF XY:

0.0294

AC XY:

21278

AN XY:

723154

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.00560

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00948

Gnomad4 FIN exome

AF:

0.0726

Gnomad4 NFE exome

AF:

0.0326

Gnomad4 OTH exome

AF:

0.0275

GnomAD4 genome

AF:

0.0250

AC:

3807

AN:

152314

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1892

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0328

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

15478-13T>C in intron 34 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 3.0% (253/8296) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs56141203). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.17

Dann

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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