rs148759448

Variant names:

• chr11-1252416-T-C
• rs148759448
• NM_002458.3:c.14937T>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.14937T>C​(p.Ile4979Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,611,078 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (65 hom., cov: 33)
  • Exomes 𝑓: 0.030 (842 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07

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=-0.89).
• BP6: Variant 11-1252416-T-C is Benign according to our data. Variant chr11-1252416-T-C is described in ClinVar as [Benign]. Clinvar id is 164001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3841/152356) while in subpopulation NFE AF= 0.0327 (2226/68022). AF 95% confidence interval is 0.0316. There are 65 homozygotes in gnomad4. There are 1908 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3841 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.14937T>C	p.Ile4979Ile	synonymous_variant	Exon 32 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.14937T>C	p.Ile4979Ile	synonymous_variant	Exon 32 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3842 AN: 152238 Hom.: 65 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0266 AC: 6542 AN: 246164 Hom.: 141 AF XY: 0.0264 AC XY: 3537 AN XY: 134046

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.00505

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00942

Gnomad FIN exome AF: 0.0743

Gnomad NFE exome AF: 0.0343

Gnomad OTH exome AF: 0.0278

GnomAD4 exome AF: 0.0301 AC: 43918 AN: 1458722 Hom.: 842 Cov.: 32 AF XY: 0.0294 AC XY: 21361 AN XY: 725544

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.00556

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00951

Gnomad4 FIN exome AF: 0.0725

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0275

GnomAD4 genome AF: 0.0252 AC: 3841 AN: 152356 Hom.: 65 Cov.: 33 AF XY: 0.0256 AC XY: 1908 AN XY: 74510

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00807

Gnomad4 FIN AF: 0.0693

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0291 Hom.: 36

Bravo AF: 0.0200

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Ile4979Ile in exon 32 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 3.2% (273/8438) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs148759448). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.076
DANN	Benign	0.51

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: rs148759448; hg19: chr11-1273646;