chr11-1228142-G-A

Variant names:

• chr11-1228142-G-A
• rs2672812
• NM_002458.3:c.774+361G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

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.774+361G>A		intron	N/A	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.774+361G>A		intron	N/A	ENSP00000436812.1
	MUC5B	ENST00000525715.5	TSL:1	n.832+361G>A		intron	N/A

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

African (AFR) AF: 0.454 AC: 18817 AN: 41470

American (AMR) AF: 0.583 AC: 8911 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3297 AN: 5128

South Asian (SAS) AF: 0.503 AC: 2428 AN: 4828

European-Finnish (FIN) AF: 0.588 AC: 6213 AN: 10574

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34122 AN: 67902

Other (OTH) AF: 0.524 AC: 1104 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.49
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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