Variant rs908229 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.2007T>C(p.Tyr669Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,597,398 control chromosomes in the GnomAD database, including 213,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20978 hom., cov: 35)

Exomes 𝑓: 0.51 ( 192122 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.577

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-1232712-T-C is Benign according to our data. Variant chr11-1232712-T-C is described in ClinVar as [Benign]. Clinvar id is 163997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 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.2007T>C	p.Tyr669Tyr	synonymous_variant	17/49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.2007T>C	p.Tyr669Tyr	synonymous_variant	17/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 linkuse as main transcript	n.2065T>C		non_coding_transcript_exon_variant	17/26	1

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79434

AN:

152014

Hom.:

20955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.514

AC:

742835

AN:

1445266

Hom.:

192122

Cov.:

AF XY:

0.513

AC XY:

367971

AN XY:

717384

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.501

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.523

AC:

79503

AN:

152132

Hom.:

20978

Cov.:

AF XY:

0.529

AC XY:

39318

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.503

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.556

Hom.:

3710

Bravo

AF:

0.523

Asia WGS

AF:

0.613

AC:

2130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Tyr669Tyr in exon 17 of MUC5B: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 40.0% (1720/4300) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs908229). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.43

DANN

Benign

0.18

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