rs56229218

Variant names:

• chr11-1255464-T-C
• rs56229218
• NM_002458.3:c.15972T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.15972T>C​(p.Leu5324Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,537,202 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (64 hom., cov: 31)
  • Exomes 𝑓: 0.011 (349 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.64

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-1255464-T-C is Benign according to our data. Variant chr11-1255464-T-C is described in ClinVar as [Benign]. Clinvar id is 178795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3774/151982) while in subpopulation NFE AF= 0.0325 (2206/67880). AF 95% confidence interval is 0.0314. There are 64 homozygotes in gnomad4. There are 1873 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.15972T>C	p.Leu5324Leu	synonymous_variant	Exon 37 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.15972T>C	p.Leu5324Leu	synonymous_variant	Exon 37 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3775 AN: 151864 Hom.: 64 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00747

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0124 AC: 2577 AN: 207460 Hom.: 59 AF XY: 0.0118 AC XY: 1334 AN XY: 113070

Gnomad AFR exome AF: 0.00979

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00668

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00284

Gnomad FIN exome AF: 0.0466

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0128

GnomAD4 exome AF: 0.0106 AC: 14721 AN: 1385220 Hom.: 349 Cov.: 35 AF XY: 0.0109 AC XY: 7504 AN XY: 688922

Gnomad4 AFR exome AF: 0.00538

Gnomad4 AMR exome AF: 0.00317

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00570

Gnomad4 FIN exome AF: 0.0653

Gnomad4 NFE exome AF: 0.00907

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0248 AC: 3774 AN: 151982 Hom.: 64 Cov.: 31 AF XY: 0.0252 AC XY: 1873 AN XY: 74310

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.00746

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00809

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0268 Hom.: 33

Bravo AF: 0.0198

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MUC5B: BP4, BP7, BS1, BS2 -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu5324Leu in exon 37 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 3.1% (256/8274) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56229218). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.29

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: rs56229218; hg19: chr11-1276694;