chr11-1247452-T-C

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.10572T>C(p.Ser3524Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,604,788 control chromosomes in the GnomAD database, including 28,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2386 hom., cov: 27)

Exomes 𝑓: 0.17 ( 26182 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.14

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=-0.95).

BP6

Variant 11-1247452-T-C is Benign according to our data. Variant chr11-1247452-T-C is described in ClinVar as Benign. ClinVar VariationId is 403164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.10572T>C	p.Ser3524Ser	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+2169A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.10572T>C	p.Ser3524Ser	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+2169A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

24283

AN:

147254

Hom.:

2385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.00517

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.152

AC:

37502

AN:

247502

AF XY:

0.156

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0830

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.00345

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.174

AC:

254180

AN:

1457416

Hom.:

26182

Cov.:

133

AF XY:

0.174

AC XY:

126298

AN XY:

725092

show subpopulations

African (AFR)

AF:

0.153

AC:

5096

AN:

33394

American (AMR)

AF:

0.0871

AC:

3891

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

4011

AN:

26096

East Asian (EAS)

AF:

0.00214

AC:

AN:

39692

South Asian (SAS)

AF:

0.149

AC:

12810

AN:

86102

European-Finnish (FIN)

AF:

0.205

AC:

10839

AN:

52852

Middle Eastern (MID)

AF:

0.162

AC:

673

AN:

4144

European-Non Finnish (NFE)

AF:

0.186

AC:

206552

AN:

1110372

Other (OTH)

AF:

0.170

AC:

10223

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

12913

25826

38739

51652

64565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7102

14204

21306

28408

35510

<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:

0.165

AC:

24294

AN:

147372

Hom.:

2386

Cov.:

AF XY:

0.163

AC XY:

11724

AN XY:

71786

show subpopulations

African (AFR)

AF:

0.157

AC:

6250

AN:

39920

American (AMR)

AF:

0.125

AC:

1865

AN:

14964

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

523

AN:

3404

East Asian (EAS)

AF:

0.00518

AC:

AN:

5022

South Asian (SAS)

AF:

0.139

AC:

633

AN:

4568

European-Finnish (FIN)

AF:

0.216

AC:

2156

AN:

9972

Middle Eastern (MID)

AF:

0.176

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.186

AC:

12310

AN:

66286

Other (OTH)

AF:

0.155

AC:

317

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

931

1862

2794

3725

4656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.174

Hom.:

1259

Bravo

AF:

0.155

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

-0.95

CADD

Benign

3.7

(source)

DANN

Benign

0.84

PhyloP100

-4.1

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