rs2672812

Positions:

• chr11-1228142-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002458.3(MUC5B):​c.774+361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,972 control chromosomes in the GnomAD database, including 19,972 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 0.51 (19972 hom., cov: 33)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.774+361G>A		intron_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.774+361G>A		intron_variant		5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.832+361G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77358 AN: 151856 Hom.: 19951 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.509 AC: 77423 AN: 151972 Hom.: 19972 Cov.: 33 AF XY: 0.516 AC XY: 38366 AN XY: 74286

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.524

Alfa AF: 0.512 Hom.: 3391

Bravo AF: 0.509

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.49

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: rs2672812; hg19: chr11-1249372; COSMIC: COSV71595830; COSMIC: COSV71595830;