rs56352092

chr11-1254363-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 178793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.15477+12C>A		intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.15477+12C>A		intron_variant		5	NM_002458.3	P1

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

GnomAD3 exomes AF: 0.0387 AC: 9107 AN: 235250 Hom.: 260 AF XY: 0.0403 AC XY: 5205 AN XY: 129270

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 SAS exome AF: 0.0714

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

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0237

Gnomad4 ASJ exome AF: 0.0832

Gnomad4 EAS exome AF: 0.00227

Gnomad4 SAS exome AF: 0.0707

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0418

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

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0641

Gnomad4 FIN AF: 0.00838

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0451 Hom.: 39

Bravo AF: 0.0521

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

15477+12C>A in intron 34 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 9.0% (378/4210) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs56352092). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.49
Dann	Benign	0.27

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: rs56352092; hg19: chr11-1275593;