Genetic Variant NM_002458.3:c.8709G>A (chr11-1245589-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002458.3(MUC5B):c.8709G>A(p.Ala2903Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,581,756 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 26)

Exomes 𝑓: 0.0026 ( 47 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -12.0

Publications

0 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 11-1245589-G-A is Benign according to our data. Variant chr11-1245589-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-12 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 47 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.8709G>A	p.Ala2903Ala	synonymous	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.57-2951C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.8709G>A	p.Ala2903Ala	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-2951C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

222

AN:

146550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000344

Gnomad ASJ

AF:

0.00410

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000227

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00152

GnomAD2 exomes

AF:

0.00155

AC:

293

AN:

189424

AF XY:

0.00164

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.000628

Gnomad ASJ exome

AF:

0.00325

Gnomad EAS exome

AF:

0.0000729

Gnomad FIN exome

AF:

0.000178

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00264

AC:

3785

AN:

1435090

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1803

AN XY:

712682

show subpopulations

African (AFR)

AF:

0.000640

AC:

AN:

32826

American (AMR)

AF:

0.000674

AC:

AN:

41520

Ashkenazi Jewish (ASJ)

AF:

0.00470

AC:

120

AN:

25550

East Asian (EAS)

AF:

0.0000513

AC:

AN:

38984

South Asian (SAS)

AF:

0.0000236

AC:

AN:

84730

European-Finnish (FIN)

AF:

0.000235

AC:

AN:

50984

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.00316

AC:

3464

AN:

1097210

Other (OTH)

AF:

0.00228

AC:

135

AN:

59208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

161

322

484

645

806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.00151

AC:

222

AN:

146666

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

71306

show subpopulations

African (AFR)

AF:

0.000763

AC:

AN:

39316

American (AMR)

AF:

0.000343

AC:

AN:

14562

Ashkenazi Jewish (ASJ)

AF:

0.00410

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.000227

AC:

AN:

4406

European-Finnish (FIN)

AF:

0.000200

AC:

AN:

10010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00250

AC:

167

AN:

66820

Other (OTH)

AF:

0.00151

AC:

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00138

Hom.:

Bravo

AF:

0.00151

ClinVar

ClinVar submissions

Significance:Benign/Likely 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

-0.99

CADD

Benign

7.3

(source)

DANN

Benign

0.74

PhyloP100

-12

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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