rs55784821

Variant names:

• chr11-1258124-G-A
• rs55784821
• NM_002458.3:c.16476G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.16476G>A​(p.Gln5492Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,594,276 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (58 hom., cov: 32)
  • Exomes 𝑓: 0.030 (812 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.369
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-1258124-G-A is Benign according to our data. Variant chr11-1258124-G-A is described in ClinVar as Benign. ClinVar VariationId is 226735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.369 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3479/152330) while in subpopulation NFE AF = 0.0327 (2227/68014). AF 95% confidence interval is 0.0316. There are 58 homozygotes in GnomAd4. There are 1736 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.16476G>A	p.Gln5492Gln	synonymous	Exon 42 of 49	NP_002449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.16476G>A	p.Gln5492Gln	synonymous	Exon 42 of 49	ENSP00000436812.1
	MUC5B	ENST00000526859.1	TSL:3	c.111G>A	p.Gln37Gln	synonymous	Exon 2 of 6	ENSP00000434539.1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3479 AN: 152212 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0253 AC: 5474 AN: 216288 AF XY: 0.0251

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0336

Gnomad OTH exome AF: 0.0253

GnomAD4 exome AF: 0.0298 AC: 43002 AN: 1441946 Hom.: 812 Cov.: 34 AF XY: 0.0292 AC XY: 20889 AN XY: 715538

African (AFR) AF: 0.00392 AC: 130 AN: 33162

American (AMR) AF: 0.00528 AC: 224 AN: 42444

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 746 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 38994

South Asian (SAS) AF: 0.00957 AC: 793 AN: 82894

European-Finnish (FIN) AF: 0.0720 AC: 3619 AN: 50268

Middle Eastern (MID) AF: 0.00437 AC: 19 AN: 4352

European-Non Finnish (NFE) AF: 0.0325 AC: 35880 AN: 1104644

Other (OTH) AF: 0.0267 AC: 1591 AN: 59520

GnomAD4 genome AF: 0.0228 AC: 3479 AN: 152330 Hom.: 58 Cov.: 32 AF XY: 0.0233 AC XY: 1736 AN XY: 74496

African (AFR) AF: 0.00553 AC: 230 AN: 41572

American (AMR) AF: 0.00686 AC: 105 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4824

European-Finnish (FIN) AF: 0.0692 AC: 736 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2227 AN: 68014

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0301 Hom.: 128

Bravo AF: 0.0172

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		0.37
PromoterAI		-0.0041	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs55784821; hg19: chr11-1279354;