chr11-1245928-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9048G>A	p.Pro3016Pro	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-3290C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9048G>A	p.Pro3016Pro	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-3290C>T		intron_variant	Intron 1 of 1	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

GnomAD2 exomes

AF:

0.0176

AC:

4393

AN:

248956

AF XY:

0.0180

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 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

African (AFR)

AF:

0.00413

AC:

138

AN:

33454

American (AMR)

AF:

0.00821

AC:

367

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

298

AN:

26110

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39678

South Asian (SAS)

AF:

0.00754

AC:

650

AN:

86228

European-Finnish (FIN)

AF:

0.0308

AC:

1639

AN:

53272

Middle Eastern (MID)

AF:

0.0219

AC:

126

AN:

5766

European-Non Finnish (NFE)

AF:

0.0268

AC:

29741

AN:

1111374

Other (OTH)

AF:

0.0218

AC:

1314

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

2327

4654

6982

9309

11636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0179

AC:

2633

AN:

147404

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1286

AN XY:

71798

show subpopulations

African (AFR)

AF:

0.00421

AC:

168

AN:

39864

American (AMR)

AF:

0.0144

AC:

213

AN:

14824

Ashkenazi Jewish (ASJ)

AF:

0.00857

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4860

South Asian (SAS)

AF:

0.00887

AC:

AN:

4622

European-Finnish (FIN)

AF:

0.0355

AC:

360

AN:

10154

Middle Eastern (MID)

AF:

0.0231

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0268

AC:

1782

AN:

66530

Other (OTH)

AF:

0.0154

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

4.9

(source)

DANN

Benign

0.56

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr11-1245928-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over