rs117336883

Variant names:

• chr11-1254324-C-T
• rs117336883
• NM_002458.3:c.15450C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId is 178792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 63 AR gene

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.15450C>T	p.Thr5150Thr	synonymous	Exon 34 of 49	NP_002449.2	Q9HC84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.15450C>T	p.Thr5150Thr	synonymous	Exon 34 of 49	ENSP00000436812.1	Q9HC84

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

GnomAD2 exomes AF: 0.0257 AC: 6201 AN: 241546 AF XY: 0.0256

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 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

African (AFR) AF: 0.0119 AC: 397 AN: 33480

American (AMR) AF: 0.00564 AC: 252 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 762 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00951 AC: 820 AN: 86252

European-Finnish (FIN) AF: 0.0725 AC: 3246 AN: 44762

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.0326 AC: 36278 AN: 1111728

Other (OTH) AF: 0.0275 AC: 1658 AN: 60312

GnomAD4 genome AF: 0.0250 AC: 3805 AN: 152324 Hom.: 63 Cov.: 33 AF XY: 0.0254 AC XY: 1893 AN XY: 74482

African (AFR) AF: 0.0131 AC: 544 AN: 41580

American (AMR) AF: 0.00745 AC: 114 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00807 AC: 39 AN: 4832

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2226 AN: 68026

Other (OTH) AF: 0.0223 AC: 47 AN: 2108

Alfa AF: 0.0298 Hom.: 108

Bravo AF: 0.0198

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0251

EpiControl AF: 0.0265

ClinVar

ClinVar submissions

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	-0.80
CADD	Benign	0.55
DANN	Benign	0.27
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117336883; hg19: chr11-1275554;