NM_002458.3:c.9617T>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.9617T>C(p.Ile3206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,602,608 control chromosomes in the GnomAD database, including 962 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 0.026 ( 69 hom., cov: 32)

Exomes 𝑓: 0.028 ( 893 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.907

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:

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 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=0.0043921173).

BP6

Variant 11-1246497-T-C is Benign according to our data. Variant chr11-1246497-T-C is described in ClinVar as [Benign]. Clinvar id is 403156.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 = 0.0257 (3763/146368) while in subpopulation NFE AF= 0.0333 (2201/66084). AF 95% confidence interval is 0.0321. There are 69 homozygotes in gnomad4. There are 1868 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9617T>C	p.Ile3206Thr	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+3124A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9617T>C	p.Ile3206Thr	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+3124A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3764

AN:

146234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00115

Gnomad AMR

AF:

0.00780

Gnomad ASJ

AF:

0.0295

Gnomad EAS

AF:

0.000421

Gnomad SAS

AF:

0.00799

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0228

GnomAD3 exomes

AF:

0.00969

AC:

2336

AN:

240968

Hom.:

112

AF XY:

0.00901

AC XY:

1177

AN XY:

130582

show subpopulations

Gnomad AFR exome

AF:

0.00772

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00265

Gnomad FIN exome

AF:

0.0420

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0277

AC:

40384

AN:

1456240

Hom.:

893

Cov.:

127

AF XY:

0.0272

AC XY:

19730

AN XY:

724588

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00905

Gnomad4 FIN exome

AF:

0.0708

Gnomad4 NFE exome

AF:

0.0297

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0257

AC:

3763

AN:

146368

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1868

AN XY:

71490

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00779

Gnomad4 ASJ

AF:

0.0295

Gnomad4 EAS

AF:

0.000421

Gnomad4 SAS

AF:

0.00800

Gnomad4 FIN

AF:

0.0708

Gnomad4 NFE

AF:

0.0333

Gnomad4 OTH

AF:

0.0225

Alfa

AF:

0.0275

Hom.:

Bravo

AF:

0.0199

ExAC

AF:

0.0227

AC:

2749

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

0.067

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.18

DANN

Benign

0.46

DEOGEN2

Benign

0.015

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00032

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.3

PrimateAI

Benign

0.23

PROVEAN

Benign

0.73

REVEL

Benign

0.0050

Sift

Benign

1.0

Vest4

0.0060

ClinPred

0.0014

GERP RS

-2.4

Varity_R

0.029

gMVP

0.089

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