Variant rs2735709 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.1596G>C(p.Leu532=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,608,528 control chromosomes in the GnomAD database, including 218,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22954 hom., cov: 34)

Exomes 𝑓: 0.52 ( 195918 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.09

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=-0.9).

BP6

Variant 11-1231478-G-C is Benign according to our data. Variant chr11-1231478-G-C is described in ClinVar as [Benign]. Clinvar id is 163995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

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.1596G>C	p.Leu532=	synonymous_variant	14/49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.1596G>C	p.Leu532=	synonymous_variant	14/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.1654G>C		non_coding_transcript_exon_variant	14/26	1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

83072

AN:

152022

Hom.:

22922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.552

GnomAD3 exomes

AF:

0.544

AC:

131192

AN:

240944

Hom.:

36049

AF XY:

0.537

AC XY:

70515

AN XY:

131328

show subpopulations

Gnomad AFR exome

AF:

0.574

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.517

AC:

752531

AN:

1456388

Hom.:

195918

Cov.:

AF XY:

0.515

AC XY:

373176

AN XY:

724264

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.575

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.523

GnomAD4 genome

AF:

0.547

AC:

83158

AN:

152140

Hom.:

22954

Cov.:

AF XY:

0.552

AC XY:

41056

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.505

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.447

Hom.:

2236

Bravo

AF:

0.551

Asia WGS

AF:

0.622

AC:

2161

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	Nov 12, 2018	- -
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

Leu532Leu in exon 14 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 49.8% (4172/8376) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2735709). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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