Variant 11-1258124-G-A 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.16476G>A(p.Gln5492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,594,276 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 58 hom., cov: 32)

Exomes 𝑓: 0.030 ( 812 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.369

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=-0.81).

BP6

Variant 11-1258124-G-A is Benign according to our data. Variant chr11-1258124-G-A is described in ClinVar as [Benign]. Clinvar id is 226735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1258124-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.369 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3479/152330) while in subpopulation NFE AF= 0.0327 (2227/68014). AF 95% confidence interval is 0.0316. There are 58 homozygotes in gnomad4. There are 1736 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16476G>A	p.Gln5492=	synonymous_variant	42/49	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.16476G>A	p.Gln5492=	synonymous_variant	42/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000526859.1 linkuse as main transcript	c.111G>A	p.Gln37=	synonymous_variant	2/6	3		ENSP00000434539

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3479

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00555

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0253

AC:

5474

AN:

216288

Hom.:

111

AF XY:

0.0251

AC XY:

2975

AN XY:

118616

show subpopulations

Gnomad AFR exome

AF:

0.00513

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00960

Gnomad FIN exome

AF:

0.0732

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0298

AC:

43002

AN:

1441946

Hom.:

812

Cov.:

AF XY:

0.0292

AC XY:

20889

AN XY:

715538

show subpopulations

Gnomad4 AFR exome

AF:

0.00392

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00957

Gnomad4 FIN exome

AF:

0.0720

Gnomad4 NFE exome

AF:

0.0325

Gnomad4 OTH exome

AF:

0.0267

GnomAD4 genome

AF:

0.0228

AC:

3479

AN:

152330

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1736

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00553

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00788

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0297

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00375

AC:

AN:

3478

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

Apr 10, 2015

p.Gln5492Gln in exon 42 of MUC5B: This variant is not expected to have clinical significance because it has been identified in 7.3% (1647/22468) of European chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs55784821). -

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

-0.81

CADD

Benign

2.5

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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