11-1246730-A-C

Position:

• chr11-1246730-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002458.3(MUC5B):​c.9850A>C​(p.Thr3284Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3284A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05448541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.9850A>C	p.Thr3284Pro	missense_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.56+2891T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.9850A>C	p.Thr3284Pro	missense_variant	31/49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2	n.56+2891T>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 128

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.28
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.060
Sift	Benign	0.28	T
Vest4		0.099
MVP		0.043
ClinPred		0.045	T
GERP RS		-4.4
Varity_R		0.058
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs2943531; hg19: chr11-1267960;