11-1222850-C-G

Variant names:

• chr11-1222850-C-G
• rs7118568
• NM_002458.3:c.-274C>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.-274C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,214 control chromosomes in the GnomAD database, including 1,751 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 0.13 (1751 hom., cov: 33)
• Consequence: MUC5B NM_002458.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.755
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.-274C>G		upstream_gene_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.-274C>G		upstream_gene_variant		5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.-216C>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20321 AN: 152096 Hom.: 1751 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.134 AC: 20340 AN: 152214 Hom.: 1751 Cov.: 33 AF XY: 0.138 AC XY: 10249 AN XY: 74400

African (AFR) AF: 0.207 AC: 8615 AN: 41540

American (AMR) AF: 0.107 AC: 1634 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 189 AN: 3472

East Asian (EAS) AF: 0.370 AC: 1903 AN: 5150

South Asian (SAS) AF: 0.142 AC: 685 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1617 AN: 10604

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0774 AC: 5261 AN: 67996

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.102 Hom.: 129

Bravo AF: 0.134

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		0.76
PromoterAI		-0.074	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7118568; hg19: chr11-1244080;