rs117336883

Positions:

• chr11-1254324-C-T

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.15450C>T​(p.Thr5150Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,605,164 control chromosomes in the GnomAD database, including 884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (63 hom., cov: 33)
  • Exomes 𝑓: 0.030 (821 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0150

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=-0.8).
• BP6: Variant 11-1254324-C-T is Benign according to our data. Variant chr11-1254324-C-T is described in ClinVar as [Benign]. Clinvar id is 178792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1254324-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.015 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3805/152324) while in subpopulation NFE AF= 0.0327 (2226/68026). AF 95% confidence interval is 0.0316. There are 63 homozygotes in gnomad4. There are 1893 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3805 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.15450C>T	p.Thr5150Thr	synonymous_variant	34/49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.15450C>T	p.Thr5150Thr	synonymous_variant	34/49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3806 AN: 152206 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00806

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0257 AC: 6201 AN: 241546 Hom.: 128 AF XY: 0.0256 AC XY: 3391 AN XY: 132270

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.00514

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00942

Gnomad FIN exome AF: 0.0752

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0275

GnomAD4 exome AF: 0.0299 AC: 43440 AN: 1452840 Hom.: 821 Cov.: 33 AF XY: 0.0293 AC XY: 21159 AN XY: 723062

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.00564

Gnomad4 ASJ exome AF: 0.0292

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: 0.0250 AC: 3805 AN: 152324 Hom.: 63 Cov.: 33 AF XY: 0.0254 AC XY: 1893 AN XY: 74482

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00807

Gnomad4 FIN AF: 0.0692

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0287 Hom.: 34

Bravo AF: 0.0198

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0251

EpiControl AF: 0.0265

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Thr5150Thr in exon 34 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% (276/8496) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs117336883). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.55
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs117336883; hg19: chr11-1275554;