chr11-1243062-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.6182C>T(p.Ala2061Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,611,446 control chromosomes in the GnomAD database, including 4,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 352 hom., cov: 30)

Exomes 𝑓: 0.057 ( 4065 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.13

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=0.001940906).

BP6

Variant 11-1243062-C-T is Benign according to our data. Variant chr11-1243062-C-T is described in ClinVar as [Benign]. Clinvar id is 403134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.6182C>T	p.Ala2061Val	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-424G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.6182C>T	p.Ala2061Val	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-424G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9379

AN:

151308

Hom.:

352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00175

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.0944

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0526

Gnomad OTH

AF:

0.0538

GnomAD3 exomes

AF:

0.0655

AC:

16269

AN:

248354

Hom.:

1037

AF XY:

0.0610

AC XY:

8216

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.0418

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.0483

Gnomad FIN exome

AF:

0.0884

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0570

AC:

83250

AN:

1460020

Hom.:

4065

Cov.:

134

AF XY:

0.0564

AC XY:

40965

AN XY:

726324

show subpopulations

Gnomad4 AFR exome

AF:

0.0623

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.0380

Gnomad4 EAS exome

AF:

0.00123

Gnomad4 SAS exome

AF:

0.0513

Gnomad4 FIN exome

AF:

0.0845

Gnomad4 NFE exome

AF:

0.0552

Gnomad4 OTH exome

AF:

0.0524

GnomAD4 genome

AF:

0.0620

AC:

9383

AN:

151426

Hom.:

352

Cov.:

AF XY:

0.0650

AC XY:

4809

AN XY:

74000

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.0944

Gnomad4 NFE

AF:

0.0526

Gnomad4 OTH

AF:

0.0532

Alfa

AF:

0.0333

Hom.:

Bravo

AF:

0.0646

ESP6500AA

AF:

0.0553

AC:

223

ESP6500EA

AF:

0.0493

AC:

412

ExAC

AF:

0.0613

AC:

7413

EpiCase

AF:

0.0498

EpiControl

AF:

0.0466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.78

DANN

Benign

0.58

DEOGEN2

Benign

0.023

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.52

REVEL

Benign

0.043

Sift

Uncertain

0.020

Vest4

0.022

ClinPred

0.0035

GERP RS

-2.0

Varity_R

0.036

gMVP

0.11

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