NM_002458.3:c.15477+11G>A

Variant names:

• chr11-1254362-G-A
• rs56088961
• NM_002458.3:c.15477+11G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.15477+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,598,328 control chromosomes in the GnomAD database, including 1,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (231 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1210 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-1254362-G-A is Benign according to our data. Variant chr11-1254362-G-A is described in ClinVar as Benign. ClinVar VariationId is 164002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.15477+11G>A		intron_variant	Intron 34 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.15477+11G>A		intron_variant	Intron 34 of 48	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7376 AN: 152168 Hom.: 228 Cov.: 33

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0388 AC: 9121 AN: 235264 AF XY: 0.0403

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.00370

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0310

Gnomad OTH exome AF: 0.0413

GnomAD4 exome AF: 0.0361 AC: 52203 AN: 1446042 Hom.: 1210 Cov.: 33 AF XY: 0.0373 AC XY: 26851 AN XY: 719528

African (AFR) AF: 0.102 AC: 3414 AN: 33458

American (AMR) AF: 0.0238 AC: 1062 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 2171 AN: 26104

East Asian (EAS) AF: 0.00227 AC: 90 AN: 39668

South Asian (SAS) AF: 0.0707 AC: 6093 AN: 86202

European-Finnish (FIN) AF: 0.0109 AC: 429 AN: 39260

Middle Eastern (MID) AF: 0.0789 AC: 455 AN: 5766

European-Non Finnish (NFE) AF: 0.0324 AC: 35975 AN: 1110696

Other (OTH) AF: 0.0418 AC: 2514 AN: 60212

GnomAD4 genome AF: 0.0486 AC: 7394 AN: 152286 Hom.: 231 Cov.: 33 AF XY: 0.0472 AC XY: 3518 AN XY: 74468

African (AFR) AF: 0.0938 AC: 3898 AN: 41546

American (AMR) AF: 0.0327 AC: 501 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.0641 AC: 309 AN: 4824

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10626

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0321 AC: 2185 AN: 68030

Other (OTH) AF: 0.0451 AC: 95 AN: 2106

Alfa AF: 0.0462 Hom.: 41

Bravo AF: 0.0521

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

15477+11G>A in intron 34 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 8.9% (375/4212) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs56088961). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56088961; hg19: chr11-1275592;