rs201778566

Positions:

chr11-1250631-C-T

Variant summary

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

The NM_002458.3(MUC5B):c.13751C>T(p.Thr4584Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 150,794 control chromosomes in the GnomAD database, including 1 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 0.020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.027 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00800

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=0.0036872923).

BP6

Variant 11-1250631-C-T is Benign according to our data. Variant chr11-1250631-C-T is described in ClinVar as [Benign]. Clinvar id is 403177.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 = 0.0198 (2991/150794) while in subpopulation NFE AF= 0.0254 (1703/67102). AF 95% confidence interval is 0.0244. There are 1 homozygotes in gnomad4. There are 1466 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2991 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.13751C>T	p.Thr4584Ile	missense_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.13751C>T	p.Thr4584Ile	missense_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

2991

AN:

150674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00630

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00666

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0178

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0270

AC:

39228

AN:

1453506

Hom.:

Cov.:

151

AF XY:

0.0263

AC XY:

19036

AN XY:

722996

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.00464

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00834

Gnomad4 FIN exome

AF:

0.0618

Gnomad4 NFE exome

AF:

0.0295

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0198

AC:

2991

AN:

150794

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1466

AN XY:

73656

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.00630

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00687

Gnomad4 FIN

AF:

0.0545

Gnomad4 NFE

AF:

0.0254

Gnomad4 OTH

AF:

0.0177

Alfa

AF:

0.0286

Hom.:

ExAC

AF:

0.0259

AC:

3129

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

Mar 28, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.6

DANN

Benign

0.87

DEOGEN2

Benign

0.025

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.69

REVEL

Benign

0.015

Sift

Uncertain

0.024

Vest4

0.041

ClinPred

0.0012

GERP RS

-1.7

Varity_R

0.033

gMVP

0.17

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