11-1244757-C-G

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.7877C>G(p.Thr2626Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,601,722 control chromosomes in the GnomAD database, including 15,824 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 0.13 ( 1492 hom., cov: 30)

Exomes 𝑓: 0.13 ( 14332 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0390

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=0.0075758398).

BP6

Variant 11-1244757-C-G is Benign according to our data. Variant chr11-1244757-C-G is described in ClinVar as [Benign]. Clinvar id is 403145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.7877C>G	p.Thr2626Arg	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-2119G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.7877C>G	p.Thr2626Arg	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-2119G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

19999

AN:

151244

Hom.:

1492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.156

AC:

37463

AN:

239454

Hom.:

3636

AF XY:

0.152

AC XY:

19713

AN XY:

129888

show subpopulations

Gnomad AFR exome

AF:

0.0955

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.0506

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.134

AC:

193845

AN:

1450360

Hom.:

14332

Cov.:

141

AF XY:

0.134

AC XY:

96693

AN XY:

721542

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.132

AC:

20007

AN:

151362

Hom.:

1492

Cov.:

AF XY:

0.139

AC XY:

10246

AN XY:

73940

show subpopulations

Gnomad4 AFR

AF:

0.0971

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.0586

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0871

Hom.:

160

Bravo

AF:

0.131

ESP6500AA

AF:

0.0845

AC:

357

ESP6500EA

AF:

0.123

AC:

1041

ExAC

AF:

0.141

AC:

17070

EpiCase

AF:

0.128

EpiControl

AF:

0.124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

0.14

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.050

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.5

REVEL

Benign

0.063

Sift

Pathogenic

0.0

Vest4

0.070

ClinPred

0.0085

GERP RS

0.12

Varity_R

0.15

gMVP

0.35

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