11-1255545-C-T

Variant names:

• chr11-1255545-C-T
• rs117452757
• NM_002458.3:c.16053C>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.16053C>T​(p.Thr5351Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,479,462 control chromosomes in the GnomAD database, including 411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T5351T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.025 (64 hom., cov: 31)
  • Exomes 𝑓: 0.010 (347 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.21
• 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=-0.79).
• BP6: Variant 11-1255545-C-T is Benign according to our data. Variant chr11-1255545-C-T is described in ClinVar as Benign. ClinVar VariationId is 164006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.21 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0247 (3753/152028) while in subpopulation NFE AF = 0.0324 (2200/67924). AF 95% confidence interval is 0.0313. There are 64 homozygotes in GnomAd4. There are 1861 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 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.16053C>T	p.Thr5351Thr	synonymous	Exon 37 of 49	NP_002449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.16053C>T	p.Thr5351Thr	synonymous	Exon 37 of 49	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3754 AN: 151910 Hom.: 64 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.0126 AC: 1822 AN: 144344 AF XY: 0.0119

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00659

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0103 AC: 13691 AN: 1327434 Hom.: 347 Cov.: 34 AF XY: 0.0105 AC XY: 6849 AN XY: 652996

African (AFR) AF: 0.00525 AC: 162 AN: 30854

American (AMR) AF: 0.00334 AC: 117 AN: 35066

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 401 AN: 24302

East Asian (EAS) AF: 0.00 AC: 0 AN: 35294

South Asian (SAS) AF: 0.00580 AC: 453 AN: 78156

European-Finnish (FIN) AF: 0.0659 AC: 3012 AN: 45704

Middle Eastern (MID) AF: 0.00220 AC: 11 AN: 5006

European-Non Finnish (NFE) AF: 0.00869 AC: 8844 AN: 1017570

Other (OTH) AF: 0.0125 AC: 691 AN: 55482

GnomAD4 genome AF: 0.0247 AC: 3753 AN: 152028 Hom.: 64 Cov.: 31 AF XY: 0.0250 AC XY: 1861 AN XY: 74306

African (AFR) AF: 0.0128 AC: 532 AN: 41476

American (AMR) AF: 0.00739 AC: 113 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4824

European-Finnish (FIN) AF: 0.0682 AC: 721 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0324 AC: 2200 AN: 67924

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.0188 Hom.: 16

Bravo AF: 0.0199

Asia WGS AF: 0.00318 AC: 11 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.55
DANN	Benign	0.41
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs117452757; hg19: chr11-1276775;