Variant 11-1230071-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_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.1287C>T(p.Gly429Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,972 control chromosomes in the GnomAD database, including 897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 57 hom., cov: 34)

Exomes 𝑓: 0.030 ( 840 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.80

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 11-1230071-C-T is Benign according to our data. Variant chr11-1230071-C-T is described in ClinVar as [Benign]. Clinvar id is 178788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3479/152278) while in subpopulation NFE AF= 0.0328 (2227/67990). AF 95% confidence interval is 0.0316. There are 57 homozygotes in gnomad4. There are 1735 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.1345C>T		non_coding_transcript_exon_variant	Exon 11 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3479

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00555

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0260

AC:

6441

AN:

247508

Hom.:

138

AF XY:

0.0259

AC XY:

3491

AN XY:

134534

show subpopulations

Gnomad AFR exome

AF:

0.00642

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00941

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0278

GnomAD4 exome

AF:

0.0300

AC:

43718

AN:

1459694

Hom.:

840

Cov.:

AF XY:

0.0293

AC XY:

21294

AN XY:

726134

show subpopulations

Gnomad4 AFR exome

AF:

0.00388

Gnomad4 AMR exome

AF:

0.00527

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00951

Gnomad4 FIN exome

AF:

0.0729

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0228

AC:

3479

AN:

152278

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1735

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00553

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0328

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0252

EpiControl

AF:

0.0264

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

Gly429Gly in exon 11 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 3.3% (271/8284) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2672810). -

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

-0.75

CADD

Benign

0.44

DANN

Benign

0.56

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