11-1246483-C-G

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.9603C>G(p.Thr3201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,608,844 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 73 hom., cov: 32)

Exomes 𝑓: 0.028 ( 894 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

Publications

1 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 (REVEL=0.009).

BP6

Variant 11-1246483-C-G is Benign according to our data. Variant chr11-1246483-C-G is described in ClinVar as Benign. ClinVar VariationId is 403155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0249 (3785/152024) while in subpopulation NFE AF = 0.0326 (2214/67932). AF 95% confidence interval is 0.0315. There are 73 homozygotes in GnomAd4. There are 1878 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9603C>G	p.Thr3201Thr	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+3138G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9603C>G	p.Thr3201Thr	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+3138G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3786

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.0292

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00791

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0222

AC:

5489

AN:

246832

AF XY:

0.0223

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.00430

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.0283

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0278

AC:

40542

AN:

1456820

Hom.:

894

Cov.:

127

AF XY:

0.0273

AC XY:

19809

AN XY:

724856

show subpopulations

African (AFR)

AF:

0.0113

AC:

378

AN:

33320

American (AMR)

AF:

0.00539

AC:

241

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

736

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00913

AC:

787

AN:

86198

European-Finnish (FIN)

AF:

0.0712

AC:

3791

AN:

53244

Middle Eastern (MID)

AF:

0.00469

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0298

AC:

33022

AN:

1107590

Other (OTH)

AF:

0.0259

AC:

1560

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2740

5479

8219

10958

13698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1172

2344

3516

4688

5860

<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:

0.0249

AC:

3785

AN:

152024

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

1878

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0130

AC:

539

AN:

41466

American (AMR)

AF:

0.00758

AC:

116

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

101

AN:

3462

East Asian (EAS)

AF:

0.000194

AC:

AN:

5154

South Asian (SAS)

AF:

0.00792

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0688

AC:

729

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0326

AC:

2214

AN:

67932

Other (OTH)

AF:

0.0218

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

163

327

490

654

817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0307

Hom.:

Bravo

AF:

0.0199

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: Frequency -

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

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.41

PhyloP100

-1.1

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