Variant rs371299435 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002458.3(MUC5B):c.8709G>A(p.Ala2903=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,581,756 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 26)

Exomes 𝑓: 0.0026 ( 47 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -12.0

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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 11-1245589-G-A is Benign according to our data. Variant chr11-1245589-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-12 with no splicing effect.

BS2

High AC in GnomAd4 at 222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.8709G>A	p.Ala2903=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.57-2951C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.8709G>A	p.Ala2903=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.57-2951C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

222

AN:

146550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000344

Gnomad ASJ

AF:

0.00410

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000227

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00152

GnomAD3 exomes

AF:

0.00155

AC:

293

AN:

189424

Hom.:

AF XY:

0.00164

AC XY:

170

AN XY:

103882

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.000628

Gnomad ASJ exome

AF:

0.00325

Gnomad EAS exome

AF:

0.0000729

Gnomad SAS exome

AF:

0.0000384

Gnomad FIN exome

AF:

0.000178

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00264

AC:

3785

AN:

1435090

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1803

AN XY:

712682

show subpopulations

Gnomad4 AFR exome

AF:

0.000640

Gnomad4 AMR exome

AF:

0.000674

Gnomad4 ASJ exome

AF:

0.00470

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.000235

Gnomad4 NFE exome

AF:

0.00316

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00151

AC:

222

AN:

146666

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

71306

show subpopulations

Gnomad4 AFR

AF:

0.000763

Gnomad4 AMR

AF:

0.000343

Gnomad4 ASJ

AF:

0.00410

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000227

Gnomad4 FIN

AF:

0.000200

Gnomad4 NFE

AF:

0.00250

Gnomad4 OTH

AF:

0.00151

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

MUC5B: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

7.3

DANN

Benign

0.74

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