rs117860519

Variant summary

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

The NM_002458.3(MUC5B):c.15218-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,610,218 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 64 hom., cov: 33)

Exomes 𝑓: 0.030 ( 838 hom. )

Consequence

MUC5B
NM_002458.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002709

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.37

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 11-1254088-G-A is Benign according to our data. Variant chr11-1254088-G-A is described in ClinVar as [Benign]. Clinvar id is 178791.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0255 (3882/152274) while in subpopulation NFE AF= 0.0327 (2225/68018). AF 95% confidence interval is 0.0316. There are 64 homozygotes in gnomad4. There are 1927 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 3883 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.15218-4G>A		splice_region_variant, 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.15218-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_002458.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3883

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0268

AC:

6542

AN:

244538

Hom.:

135

AF XY:

0.0265

AC XY:

3538

AN XY:

133570

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.00525

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00936

Gnomad FIN exome

AF:

0.0759

Gnomad NFE exome

AF:

0.0345

Gnomad OTH exome

AF:

0.0284

GnomAD4 exome

AF:

0.0302

AC:

44007

AN:

1457944

Hom.:

838

Cov.:

AF XY:

0.0295

AC XY:

21425

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00954

Gnomad4 FIN exome

AF:

0.0731

Gnomad4 NFE exome

AF:

0.0326

Gnomad4 OTH exome

AF:

0.0278

GnomAD4 genome

AF:

0.0255

AC:

3882

AN:

152274

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1927

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0293

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0251

EpiControl

AF:

0.0265

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

15218-4G>A in intron 33 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 3.2% (268/8444) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs117860519). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

Cadd

Benign

0.018

Dann

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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