NM_002458.3:c.3297+409A>G

Variant names:

• chr11-1237573-A-G
• rs2014486
• NM_002458.3:c.3297+409A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002458.3(MUC5B):​c.3297+409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,152 control chromosomes in the GnomAD database, including 20,980 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20980 hom., cov: 33)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.3297+409A>G		intron	N/A	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.3297+409A>G		intron	N/A	ENSP00000436812.1
	MUC5B	ENST00000525715.5	TSL:1	n.3355+409A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79458 AN: 152034 Hom.: 20956 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79529 AN: 152152 Hom.: 20980 Cov.: 33 AF XY: 0.529 AC XY: 39323 AN XY: 74362

African (AFR) AF: 0.497 AC: 20633 AN: 41508

American (AMR) AF: 0.587 AC: 8987 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1899 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3433 AN: 5182

South Asian (SAS) AF: 0.507 AC: 2448 AN: 4828

European-Finnish (FIN) AF: 0.587 AC: 6201 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34159 AN: 67986

Other (OTH) AF: 0.536 AC: 1130 AN: 2108

Alfa AF: 0.514 Hom.: 46797

Bravo AF: 0.523

Asia WGS AF: 0.615 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		0.055
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: rs2014486; hg19: chr11-1258803;