dbSNP rs56069229: MUC5B:c.1103-11G>C (chr11-1229679-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.1103-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,552,274 control chromosomes in the GnomAD database, including 831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 57 hom., cov: 34)

Exomes 𝑓: 0.030 ( 774 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Splicing: ADA: 0.00001679

Clinical Significance

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

Conservation

PhyloP100: -1.18

Publications

3 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 Gene-Disease associations (from GenCC):

interstitial lung disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MUC5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-1229679-G-C is Benign according to our data. Variant chr11-1229679-G-C is described in ClinVar as Benign. ClinVar VariationId is 178787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3477/152266) while in subpopulation NFE AF = 0.0327 (2221/67988). AF 95% confidence interval is 0.0315. There are 57 homozygotes in GnomAd4. There are 1736 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.1103-11G>C		intron	N/A	NP_002449.2	Q9HC84

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.1103-11G>C	intron	N/A	ENSP00000436812.1	Q9HC84
MUC5B	ENST00000525715.5	TSL:1	n.1161-11G>C	intron	N/A
MUC5B	ENST00000531082.1	TSL:3	n.373-11G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3477

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00557

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0228

AC:

3655

AN:

160586

AF XY:

0.0225

show subpopulations

Gnomad AFR exome

AF:

0.00542

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0695

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0296

AC:

41459

AN:

1400008

Hom.:

774

Cov.:

AF XY:

0.0290

AC XY:

20059

AN XY:

692098

show subpopulations

African (AFR)

AF:

0.00392

AC:

125

AN:

31924

American (AMR)

AF:

0.00542

AC:

204

AN:

37640

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

731

AN:

25290

East Asian (EAS)

AF:

0.00

AC:

AN:

36364

South Asian (SAS)

AF:

0.00987

AC:

791

AN:

80168

European-Finnish (FIN)

AF:

0.0708

AC:

2727

AN:

38536

Middle Eastern (MID)

AF:

0.00458

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0325

AC:

35325

AN:

1086010

Other (OTH)

AF:

0.0262

AC:

1530

AN:

58394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2230

4460

6689

8919

11149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1318

2636

3954

5272

6590

<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:

0.0228

AC:

3477

AN:

152266

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1736

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00556

AC:

231

AN:

41558

American (AMR)

AF:

0.00680

AC:

104

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00849

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0694

AC:

737

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0327

AC:

2221

AN:

67988

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

186

373

559

746

932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0188

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.54

(source)

DANN

Benign

0.43

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over