11-1247725-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.10845C>T(p.Leu3615Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,588,130 control chromosomes in the GnomAD database, including 23,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1831 hom., cov: 27)

Exomes 𝑓: 0.14 ( 21296 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.44

Publications

5 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=-0.87).

BP6

Variant 11-1247725-C-T is Benign according to our data. Variant chr11-1247725-C-T is described in ClinVar as Benign. ClinVar VariationId is 403166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.10845C>T	p.Leu3615Leu	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1 link	n.56+1896G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.10845C>T	p.Leu3615Leu	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2 link	n.56+1896G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

19679

AN:

147658

Hom.:

1831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0609

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.162

AC:

37149

AN:

229864

AF XY:

0.156

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0552

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.137

AC:

198015

AN:

1440354

Hom.:

21296

Cov.:

AF XY:

0.138

AC XY:

98764

AN XY:

716232

show subpopulations

African (AFR)

AF:

0.0834

AC:

2770

AN:

33230

American (AMR)

AF:

0.282

AC:

12349

AN:

43808

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3453

AN:

25762

East Asian (EAS)

AF:

0.104

AC:

4114

AN:

39390

South Asian (SAS)

AF:

0.146

AC:

12483

AN:

85620

European-Finnish (FIN)

AF:

0.227

AC:

11733

AN:

51592

Middle Eastern (MID)

AF:

0.148

AC:

609

AN:

4108

European-Non Finnish (NFE)

AF:

0.130

AC:

142814

AN:

1097344

Other (OTH)

AF:

0.129

AC:

7690

AN:

59500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.586

Heterozygous variant carriers

8480

16960

25439

33919

42399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5022

10044

15066

20088

25110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.133

AC:

19674

AN:

147776

Hom.:

1831

Cov.:

AF XY:

0.140

AC XY:

10102

AN XY:

71996

show subpopulations

African (AFR)

AF:

0.0870

AC:

3534

AN:

40598

American (AMR)

AF:

0.206

AC:

3097

AN:

15032

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

479

AN:

3406

East Asian (EAS)

AF:

0.0611

AC:

299

AN:

4894

South Asian (SAS)

AF:

0.145

AC:

669

AN:

4628

European-Finnish (FIN)

AF:

0.244

AC:

2435

AN:

9992

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8707

AN:

66010

Other (OTH)

AF:

0.127

AC:

257

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

650

1299

1949

2598

3248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0930

Hom.:

260

Bravo

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.82

PhyloP100

-7.4

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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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