dbSNP rs200948102: MUC5B:p.Ala3318Ala (chr11-1246834-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.9954C>T(p.Ala3318Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,597,310 control chromosomes in the GnomAD database, including 76,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 3714 hom., cov: 28)

Exomes 𝑓: 0.31 ( 72320 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.144

Publications

8 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.02).

BP6

Variant 11-1246834-C-T is Benign according to our data. Variant chr11-1246834-C-T is described in ClinVar as Benign. ClinVar VariationId is 403160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.144 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

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.9954C>T	p.Ala3318Ala	synonymous	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.56+2787G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.9954C>T	p.Ala3318Ala	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+2787G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

38903

AN:

146410

Hom.:

3708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.291

AC:

62944

AN:

216614

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.578

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.311

AC:

451115

AN:

1450778

Hom.:

72320

Cov.:

118

AF XY:

0.310

AC XY:

223506

AN XY:

721894

show subpopulations

African (AFR)

AF:

0.209

AC:

6959

AN:

33370

American (AMR)

AF:

0.304

AC:

13565

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7461

AN:

25986

East Asian (EAS)

AF:

0.570

AC:

22285

AN:

39098

South Asian (SAS)

AF:

0.281

AC:

24192

AN:

86056

European-Finnish (FIN)

AF:

0.288

AC:

15215

AN:

52888

Middle Eastern (MID)

AF:

0.266

AC:

1399

AN:

5250

European-Non Finnish (NFE)

AF:

0.309

AC:

341472

AN:

1103640

Other (OTH)

AF:

0.310

AC:

18567

AN:

59902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

20273

40546

60820

81093

101366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11206

22412

33618

44824

56030

<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:

0.266

AC:

38934

AN:

146532

Hom.:

3714

Cov.:

AF XY:

0.268

AC XY:

19141

AN XY:

71498

show subpopulations

African (AFR)

AF:

0.201

AC:

8136

AN:

40496

American (AMR)

AF:

0.298

AC:

4367

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

922

AN:

3366

East Asian (EAS)

AF:

0.495

AC:

2287

AN:

4620

South Asian (SAS)

AF:

0.260

AC:

1204

AN:

4630

European-Finnish (FIN)

AF:

0.265

AC:

2667

AN:

10062

Middle Eastern (MID)

AF:

0.238

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.281

AC:

18395

AN:

65474

Other (OTH)

AF:

0.291

AC:

593

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1326

2652

3977

5303

6629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.285

Hom.:

968

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.69

PhyloP100

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over