chr11-1247701-A-C

Variant names:

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.10821A>C(p.Ala3607Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,315,020 control chromosomes in the GnomAD database, including 96,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8667 hom., cov: 26)

Exomes 𝑓: 0.24 ( 88289 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.66

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 11-1247701-A-C is Benign according to our data. Variant chr11-1247701-A-C is described in ClinVar as Benign. ClinVar VariationId is 403165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.66 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8667 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.10821A>C	p.Ala3607Ala	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.56+1920T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.10821A>C	p.Ala3607Ala	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+1920T>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

47027

AN:

140838

Hom.:

8652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.378

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.282

AC:

54820

AN:

194570

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.236

AC:

276554

AN:

1174056

Hom.:

88289

Cov.:

110

AF XY:

0.238

AC XY:

139730

AN XY:

587684

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.225

AC:

6293

AN:

27910

American (AMR)

AF:

0.238

AC:

8977

AN:

37780

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

6785

AN:

21948

East Asian (EAS)

AF:

0.560

AC:

20516

AN:

36606

South Asian (SAS)

AF:

0.278

AC:

20604

AN:

74012

European-Finnish (FIN)

AF:

0.243

AC:

11256

AN:

46300

Middle Eastern (MID)

AF:

0.283

AC:

993

AN:

3506

European-Non Finnish (NFE)

AF:

0.214

AC:

187510

AN:

875708

Other (OTH)

AF:

0.271

AC:

13620

AN:

50286

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.353

Heterozygous variant carriers

7777

15555

23332

31110

38887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2914

5828

8742

11656

14570

<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:

0.334

AC:

47088

AN:

140964

Hom.:

8667

Cov.:

AF XY:

0.331

AC XY:

22683

AN XY:

68496

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.312

AC:

11933

AN:

38262

American (AMR)

AF:

0.352

AC:

5089

AN:

14450

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1222

AN:

3252

East Asian (EAS)

AF:

0.577

AC:

2615

AN:

4534

South Asian (SAS)

AF:

0.319

AC:

1382

AN:

4326

European-Finnish (FIN)

AF:

0.281

AC:

2727

AN:

9704

Middle Eastern (MID)

AF:

0.371

AC:

106

AN:

286

European-Non Finnish (NFE)

AF:

0.332

AC:

21052

AN:

63402

Other (OTH)

AF:

0.351

AC:

664

AN:

1892

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

1468

2937

4405

5874

7342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.244

Hom.:

952

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

(source)

DANN

Benign

0.43

PhyloP100

-5.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over