rs56352092

Variant names:

• chr11-1254363-C-A
• rs56352092
• NM_002458.3:c.15477+12C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.15477+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,598,332 control chromosomes in the GnomAD database, including 1,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (231 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1211 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-1254363-C-A is Benign according to our data. Variant chr11-1254363-C-A is described in ClinVar as Benign. ClinVar VariationId is 178793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.15477+12C>A		intron	N/A	NP_002449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.15477+12C>A		intron	N/A	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7376 AN: 152174 Hom.: 228 Cov.: 33

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0387 AC: 9107 AN: 235250 AF XY: 0.0403

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.00370

Gnomad FIN exome AF: 0.0100

Gnomad NFE exome AF: 0.0309

Gnomad OTH exome AF: 0.0414

GnomAD4 exome AF: 0.0361 AC: 52202 AN: 1446040 Hom.: 1211 Cov.: 33 AF XY: 0.0373 AC XY: 26851 AN XY: 719528

African (AFR) AF: 0.102 AC: 3414 AN: 33460

American (AMR) AF: 0.0237 AC: 1061 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 2173 AN: 26104

East Asian (EAS) AF: 0.00227 AC: 90 AN: 39670

South Asian (SAS) AF: 0.0707 AC: 6093 AN: 86194

European-Finnish (FIN) AF: 0.0109 AC: 427 AN: 39264

Middle Eastern (MID) AF: 0.0789 AC: 455 AN: 5766

European-Non Finnish (NFE) AF: 0.0324 AC: 35975 AN: 1110696

Other (OTH) AF: 0.0418 AC: 2514 AN: 60212

GnomAD4 genome AF: 0.0486 AC: 7394 AN: 152292 Hom.: 231 Cov.: 33 AF XY: 0.0472 AC XY: 3518 AN XY: 74470

African (AFR) AF: 0.0938 AC: 3898 AN: 41552

American (AMR) AF: 0.0327 AC: 501 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.0641 AC: 309 AN: 4822

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10624

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0321 AC: 2185 AN: 68022

Other (OTH) AF: 0.0451 AC: 95 AN: 2106

Alfa AF: 0.0462 Hom.: 41

Bravo AF: 0.0521

Asia WGS AF: 0.0400 AC: 138 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	-0.89
CADD	Benign	0.49
DANN	Benign	0.27
PhyloP100		-1.0
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: rs56352092; hg19: chr11-1275593;