chr11-1248397-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.11517C>T(p.Thr3839Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,610,678 control chromosomes in the GnomAD database, including 82,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7216 hom., cov: 28)

Exomes 𝑓: 0.31 ( 75222 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.75

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 11-1248397-C-T is Benign according to our data. Variant chr11-1248397-C-T is described in ClinVar as [Benign]. Clinvar id is 403168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.11517C>T	p.Thr3839Thr	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+1224G>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.11517C>T	p.Thr3839Thr	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+1224G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44043

AN:

149726

Hom.:

7202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.321

AC:

79898

AN:

248846

Hom.:

13871

AF XY:

0.320

AC XY:

43182

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.608

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.314

AC:

458103

AN:

1460832

Hom.:

75222

Cov.:

150

AF XY:

0.312

AC XY:

226727

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.294

AC:

44076

AN:

149846

Hom.:

7216

Cov.:

AF XY:

0.295

AC XY:

21619

AN XY:

73168

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.301

Hom.:

2210

Bravo

AF:

0.294

EpiCase

AF:

0.312

EpiControl

AF:

0.314

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

- -

Nov 12, 2018

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

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.1

DANN

Benign

0.60

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