Variant chr11-1257566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.16306G>A(p.Val5436Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,607,968 control chromosomes in the GnomAD database, including 884 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 57 hom., cov: 32)

Exomes 𝑓: 0.030 ( 827 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00300

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031365752).

BP6

Variant 11-1257566-G-A is Benign according to our data. Variant chr11-1257566-G-A is described in ClinVar as [Benign]. Clinvar id is 164009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1257566-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3479/152290) while in subpopulation NFE AF= 0.0328 (2228/68016). AF 95% confidence interval is 0.0316. There are 57 homozygotes in gnomad4. There are 1737 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	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16306G>A	p.Val5436Met	missense_variant	41/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.16306G>A	p.Val5436Met	missense_variant	41/49	5	NM_002458.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3479

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00557

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00809

Gnomad FIN

AF:

0.0690

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0254

AC:

6197

AN:

243876

Hom.:

126

AF XY:

0.0254

AC XY:

3382

AN XY:

133286

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.00485

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00942

Gnomad FIN exome

AF:

0.0740

Gnomad NFE exome

AF:

0.0345

Gnomad OTH exome

AF:

0.0271

GnomAD4 exome

AF:

0.0298

AC:

43348

AN:

1455678

Hom.:

827

Cov.:

AF XY:

0.0292

AC XY:

21121

AN XY:

724348

show subpopulations

Gnomad4 AFR exome

AF:

0.00391

Gnomad4 AMR exome

AF:

0.00521

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00952

Gnomad4 FIN exome

AF:

0.0718

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0228

AC:

3479

AN:

152290

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1737

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00556

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.0690

Gnomad4 NFE

AF:

0.0328

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0172

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0330

AC:

127

ESP6500AA

AF:

0.00746

AC:

ESP6500EA

AF:

0.0317

AC:

269

ExAC

AF:

0.0270

AC:

3256

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0252

EpiControl

AF:

0.0264

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

Val5436Met in exon 41 of MUC5B: This variant is not expected to have clinical si gnificance because it has been identified in 3.2% (269/8482) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs55657020). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.021

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

REVEL

Benign

0.037

Sift

Benign

0.12

Vest4

0.10

ClinPred

0.0092

GERP RS

0.71

Varity_R

0.042

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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