chr11-1255193-G-C

Variant names:

Variant summary

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

The NM_002458.3(MUC5B):c.15817G>C(p.Ala5273Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,487,052 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 63 hom., cov: 31)

Exomes 𝑓: 0.030 ( 763 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.39

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002364099).

BP6

Variant 11-1255193-G-C is Benign according to our data. Variant chr11-1255193-G-C is described in ClinVar as [Benign]. Clinvar id is 164005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0286 (3594/125626) while in subpopulation NFE AF= 0.0359 (2159/60164). AF 95% confidence interval is 0.0346. There are 63 homozygotes in gnomad4. There are 1759 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.15817G>C	p.Ala5273Pro	missense_variant	Exon 36 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.15817G>C	p.Ala5273Pro	missense_variant	Exon 36 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

3595

AN:

125572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00983

Gnomad ASJ

AF:

0.0301

Gnomad EAS

AF:

0.000220

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0859

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0242

AC:

3670

AN:

151624

Hom.:

AF XY:

0.0238

AC XY:

1930

AN XY:

81210

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.00526

Gnomad ASJ exome

AF:

0.0273

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00981

Gnomad FIN exome

AF:

0.0716

Gnomad NFE exome

AF:

0.0307

Gnomad OTH exome

AF:

0.0229

GnomAD4 exome

AF:

0.0297

AC:

40417

AN:

1361426

Hom.:

763

Cov.:

AF XY:

0.0290

AC XY:

19517

AN XY:

671894

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.00600

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00984

Gnomad4 FIN exome

AF:

0.0745

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.0286

AC:

3594

AN:

125626

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

1759

AN XY:

60384

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.00982

Gnomad4 ASJ

AF:

0.0301

Gnomad4 EAS

AF:

0.000221

Gnomad4 SAS

AF:

0.00810

Gnomad4 FIN

AF:

0.0859

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0266

Alfa

AF:

0.0252

Hom.:

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0330

AC:

127

ExAC

AF:

0.00670

AC:

704

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala5273Pro in exon 36 of MUC5B: This variant is not expected to have clinical si gnificance because it has been identified in 8.1% (15/186) of Finnish chromosome s from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.g ov/projects/SNP; dbSNP rs56123928). -

May 22, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.012

DANN

Benign

0.22

DEOGEN2

Benign

0.014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.83

PrimateAI

Benign

0.34

PROVEAN

Benign

0.24

REVEL

Benign

0.0050

Sift

Benign

0.30

Vest4

0.068

ClinPred

0.00054

GERP RS

-2.8

Varity_R

0.040

gMVP

0.24

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