11-1256199-C-T

Variant names:

• chr11-1256199-C-T
• rs55845452
• NM_002458.3:c.16110C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002458.3(MUC5B):​c.16110C>T​(p.Pro5370Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 582,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P5370P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.21
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-4.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.16110C>T	p.Pro5370Pro	synonymous_variant	Exon 38 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.16110C>T	p.Pro5370Pro	synonymous_variant	Exon 38 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000172 AC: 1 AN: 582316 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 315208

African (AFR) AF: 0.00 AC: 0 AN: 16224

American (AMR) AF: 0.00 AC: 0 AN: 37372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20242

East Asian (EAS) AF: 0.00 AC: 0 AN: 32882

South Asian (SAS) AF: 0.00 AC: 0 AN: 63880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4112

European-Non Finnish (NFE) AF: 0.00000306 AC: 1 AN: 327258

Other (OTH) AF: 0.00 AC: 0 AN: 31474

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.045
DANN	Benign	0.58
PhyloP100		-4.2

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: rs55845452; hg19: chr11-1277429;