chr11-1245928-G-A

Position:

chr11-1245928-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.9048G>A(p.Pro3016Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,608,322 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 38 hom., cov: 29)

Exomes 𝑓: 0.023 ( 561 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.67

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:):

MUC5B-AS1 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=-0.99).

BP6

Variant 11-1245928-G-A is Benign according to our data. Variant chr11-1245928-G-A is described in ClinVar as [Benign]. Clinvar id is 403149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0179 (2633/147404) while in subpopulation NFE AF= 0.0268 (1782/66530). AF 95% confidence interval is 0.0257. There are 38 homozygotes in gnomad4. There are 1286 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.9048G>A	p.Pro3016Pro	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.57-3290C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.9048G>A	p.Pro3016Pro	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.57-3290C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2633

AN:

147280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00423

Gnomad AMI

AF:

0.00336

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.00857

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00886

Gnomad FIN

AF:

0.0355

Gnomad MID

AF:

0.0219

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0155

GnomAD3 exomes

AF:

0.0176

AC:

4393

AN:

248956

Hom.:

AF XY:

0.0180

AC XY:

2430

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.00342

Gnomad AMR exome

AF:

0.00762

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00759

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0235

AC:

34275

AN:

1460918

Hom.:

561

Cov.:

AF XY:

0.0230

AC XY:

16696

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.00413

Gnomad4 AMR exome

AF:

0.00821

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00754

Gnomad4 FIN exome

AF:

0.0308

Gnomad4 NFE exome

AF:

0.0268

Gnomad4 OTH exome

AF:

0.0218

GnomAD4 genome

AF:

0.0179

AC:

2633

AN:

147404

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1286

AN XY:

71798

show subpopulations

Gnomad4 AFR

AF:

0.00421

Gnomad4 AMR

AF:

0.0144

Gnomad4 ASJ

AF:

0.00857

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00887

Gnomad4 FIN

AF:

0.0355

Gnomad4 NFE

AF:

0.0268

Gnomad4 OTH

AF:

0.0154

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0243

EpiControl

AF:

0.0250

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

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 in splice consensus -

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

-0.99

CADD

Benign

4.9

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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