Variant 11-1227730-G-A 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.723G>A(p.Thr241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 723,098 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 345 hom., cov: 34)

Exomes 𝑓: 0.077 ( 1949 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.20

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:

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=-0.75).

BP6

Variant 11-1227730-G-A is Benign according to our data. Variant chr11-1227730-G-A is described in ClinVar as [Benign]. Clinvar id is 178783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.723G>A	p.Thr241=	synonymous_variant	7/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.723G>A	p.Thr241=	synonymous_variant	7/49	5	NM_002458.3	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.781G>A		non_coding_transcript_exon_variant	7/26	1

Frequencies

GnomAD3 genomes

AF:

0.0621

AC:

9455

AN:

152176

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0891

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0679

GnomAD3 exomes

AF:

0.0792

AC:

12912

AN:

163074

Hom.:

619

AF XY:

0.0786

AC XY:

6823

AN XY:

86816

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.0836

Gnomad EAS exome

AF:

0.0453

Gnomad SAS exome

AF:

0.0780

Gnomad FIN exome

AF:

0.0999

Gnomad NFE exome

AF:

0.0697

Gnomad OTH exome

AF:

0.0765

GnomAD4 exome

AF:

0.0773

AC:

44102

AN:

570804

Hom.:

1949

Cov.:

AF XY:

0.0774

AC XY:

23857

AN XY:

308344

show subpopulations

Gnomad4 AFR exome

AF:

0.0292

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.0845

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0678

Gnomad4 OTH exome

AF:

0.0685

GnomAD4 genome

AF:

0.0620

AC:

9448

AN:

152294

Hom.:

345

Cov.:

AF XY:

0.0649

AC XY:

4830

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.0889

Gnomad4 ASJ

AF:

0.0919

Gnomad4 EAS

AF:

0.0522

Gnomad4 SAS

AF:

0.0792

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0675

Gnomad4 OTH

AF:

0.0667

Alfa

AF:

0.0655

Hom.:

148

Bravo

AF:

0.0607

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Thr241Thr in exon 7 of MUC5B: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 6.0% (483/8038) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs2075855). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.059

DANN

Benign

0.73

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