Variant 11-1228722-C-T 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.933C>T(p.His311His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,524,960 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0050 ( 28 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56

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 (HGNC:):

MUC5B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 11-1228722-C-T is Benign according to our data. Variant chr11-1228722-C-T is described in ClinVar as [Benign]. Clinvar id is 178785.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BS2

High AC in GnomAd4 at 986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.933C>T	p.His311His	synonymous_variant	8/49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.933C>T	p.His311His	synonymous_variant	8/49	5	NM_002458.3	ENSP00000436812.1	Q9HC84
MUC5B	ENST00000525715.5 linkuse as main transcript	n.991C>T		non_coding_transcript_exon_variant	8/26	1
MUC5B	ENST00000531082.1 linkuse as main transcript	n.203C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00465

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00455

AC:

613

AN:

134602

Hom.:

AF XY:

0.00420

AC XY:

307

AN XY:

73074

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.0000939

Gnomad SAS exome

AF:

0.0000448

Gnomad FIN exome

AF:

0.00279

Gnomad NFE exome

AF:

0.00534

Gnomad OTH exome

AF:

0.00688

GnomAD4 exome

AF:

0.00498

AC:

6831

AN:

1372686

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3321

AN XY:

675234

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.00374

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.0000565

Gnomad4 SAS exome

AF:

0.0000889

Gnomad4 FIN exome

AF:

0.00279

Gnomad4 NFE exome

AF:

0.00512

Gnomad4 OTH exome

AF:

0.00620

GnomAD4 genome

AF:

0.00648

AC:

986

AN:

152274

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00465

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00463

Hom.:

Bravo

AF:

0.00681

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

His311His in exon 8 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 0.8% (28/3324) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs145446448). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.12

DANN

Benign

0.93

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