Variant 11-1247725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002458.3(MUC5B):c.10845C>T(p.Leu3615Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,588,130 control chromosomes in the GnomAD database, including 23,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1831 hom., cov: 27)

Exomes 𝑓: 0.14 ( 21296 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.44

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:):

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=-0.87).

BP6

Variant 11-1247725-C-T is Benign according to our data. Variant chr11-1247725-C-T is described in ClinVar as [Benign]. Clinvar id is 403166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.10845C>T	p.Leu3615Leu	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.56+1896G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.10845C>T	p.Leu3615Leu	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.56+1896G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

19679

AN:

147658

Hom.:

1831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0609

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.162

AC:

37149

AN:

229864

Hom.:

4862

AF XY:

0.156

AC XY:

19622

AN XY:

125622

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0552

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.137

AC:

198015

AN:

1440354

Hom.:

21296

Cov.:

AF XY:

0.138

AC XY:

98764

AN XY:

716232

show subpopulations

Gnomad4 AFR exome

AF:

0.0834

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.133

AC:

19674

AN:

147776

Hom.:

1831

Cov.:

AF XY:

0.140

AC XY:

10102

AN XY:

71996

show subpopulations

Gnomad4 AFR

AF:

0.0870

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0611

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0923

Hom.:

253

Bravo

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

DANN

Benign

0.82

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