11-1237053-G-T

Variant names:

• chr11-1237053-G-T
• rs78669250
• NM_002458.3:c.3186G>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.3186G>T​(p.Pro1062Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,586 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. P1062P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60
• 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=-0.82).
• BP7: Synonymous conserved (PhyloP=-3.6 with no splicing effect.

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.3186G>T	p.Pro1062Pro	synonymous	Exon 25 of 49	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.3186G>T	p.Pro1062Pro	synonymous	Exon 25 of 49	ENSP00000436812.1
	MUC5B	ENST00000525715.5	TSL:1	n.3244G>T		non_coding_transcript_exon	Exon 25 of 26

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428586 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708530

African (AFR) AF: 0.00 AC: 0 AN: 32336

American (AMR) AF: 0.00 AC: 0 AN: 40774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25072

East Asian (EAS) AF: 0.00 AC: 0 AN: 37762

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094242

Other (OTH) AF: 0.00 AC: 0 AN: 58956

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.034
DANN	Benign	0.42
PhyloP100		-3.6

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: rs78669250; hg19: chr11-1258283; COSMIC: COSV71594415;