Genetic Variant MUC5B:p.Asn1859Asn (chr11-1242457-C-T) – ACMG Classification: Benign (-21 pts)

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.5577C>T(p.Asn1859Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,613,718 control chromosomes in the GnomAD database, including 2,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 179 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2084 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.59

Publications

7 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=-0.79).

BP6

Variant 11-1242457-C-T is Benign according to our data. Variant chr11-1242457-C-T is described in ClinVar as [Benign]. Clinvar id is 1230323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.5577C>T	p.Asn1859Asn	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.238G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.5577C>T	p.Asn1859Asn	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.238G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0391

AC:

5946

AN:

152010

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0526

Gnomad OTH

AF:

0.0268

GnomAD2 exomes

AF:

0.0408

AC:

10157

AN:

249190

AF XY:

0.0417

show subpopulations

Gnomad AFR exome

AF:

0.00740

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0482

AC:

70484

AN:

1461590

Hom.:

2084

Cov.:

AF XY:

0.0474

AC XY:

34498

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.00657

AC:

220

AN:

33480

American (AMR)

AF:

0.0173

AC:

772

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0217

AC:

566

AN:

26132

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0189

AC:

1627

AN:

86258

European-Finnish (FIN)

AF:

0.110

AC:

5896

AN:

53366

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0530

AC:

58889

AN:

1111816

Other (OTH)

AF:

0.0406

AC:

2451

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5008

10016

15025

20033

25041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0391

AC:

5945

AN:

152128

Hom.:

179

Cov.:

AF XY:

0.0416

AC XY:

3095

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00959

AC:

398

AN:

41486

American (AMR)

AF:

0.0270

AC:

413

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0158

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.123

AC:

1300

AN:

10584

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0526

AC:

3574

AN:

67966

Other (OTH)

AF:

0.0265

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

290

580

870

1160

1450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0451

Hom.:

Bravo

AF:

0.0300

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

(source)

DANN

Benign

0.89

PhyloP100

-4.6

Mutation Taster

=97/3

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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11-1242457-C-T

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