Variant chr11-1229258-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.1065C>T(p.Cys355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,586,682 control chromosomes in the GnomAD database, including 109,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10199 hom., cov: 33)

Exomes 𝑓: 0.37 ( 99316 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.118

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=-0.52).

BP6

Variant 11-1229258-C-T is Benign according to our data. Variant chr11-1229258-C-T is described in ClinVar as [Benign]. Clinvar id is 178786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 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.1065C>T	p.Cys355=	synonymous_variant	9/49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MUC5B	ENST00000529681.5 linkuse as main transcript	c.1065C>T	p.Cys355=	synonymous_variant	9/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.1123C>T		non_coding_transcript_exon_variant	9/26	1
MUC5B	ENST00000531082.1 linkuse as main transcript	n.335C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54721

AN:

151892

Hom.:

10182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.371

GnomAD3 exomes

AF:

0.387

AC:

81495

AN:

210640

Hom.:

16152

AF XY:

0.380

AC XY:

43649

AN XY:

114902

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.370

AC:

530320

AN:

1434672

Hom.:

99316

Cov.:

AF XY:

0.367

AC XY:

261566

AN XY:

712066

show subpopulations

Gnomad4 AFR exome

AF:

0.282

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.596

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.364

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.360

AC:

54771

AN:

152010

Hom.:

10199

Cov.:

AF XY:

0.364

AC XY:

27073

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.342

Gnomad4 EAS

AF:

0.603

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.376

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.363

Hom.:

17342

Bravo

AF:

0.364

Asia WGS

AF:

0.510

AC:

1773

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

Cys355Cys in exon 9 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 34.7% (2915/8394) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2075859). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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