Variant 11-1242418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002458.3(MUC5B):c.5538G>A(p.Val1846=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,874 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-1242418-G-A is Benign according to our data. Variant chr11-1242418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641205.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.29 with no splicing effect.

BS2

High AC in GnomAd4 at 328 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.5538G>A	p.Val1846=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.277C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.5538G>A	p.Val1846=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.277C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00183

AC:

456

AN:

249106

Hom.:

AF XY:

0.00158

AC XY:

213

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.000516

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000696

Gnomad NFE exome

AF:

0.00352

Gnomad OTH exome

AF:

0.000992

GnomAD4 exome

AF:

0.00325

AC:

4747

AN:

1461616

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

2238

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.00410

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152258

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00242

Hom.:

Bravo

AF:

0.00198

EpiCase

AF:

0.00398

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

MUC5B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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