rs202088302

Variant names:

• chr11-1250554-T-C
• rs202088302
• NM_002458.3:c.13674T>C
• MUC5B p.Thr4558Thr

Your query was ambiguous. Multiple possible variants found:

• chr11-1250554-T-C
• chr11-1250554-T-G

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.13674T>C​(p.Thr4558Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,609,898 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (47 hom., cov: 31)
  • Exomes 𝑓: 0.030 (823 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.90
• 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=-1.02).
• BP6: Variant 11-1250554-T-C is Benign according to our data. Variant chr11-1250554-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 403192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.9 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0251 (3720/148368) while in subpopulation NFE AF = 0.0326 (2184/67088). AF 95% confidence interval is 0.0314. There are 47 homozygotes in GnomAd4. There are 1844 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 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.13674T>C	p.Thr4558Thr	synonymous	Exon 31 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.13674T>C	p.Thr4558Thr	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3721 AN: 148244 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00741

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00816

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0232

GnomAD2 exomes AF: 0.0268 AC: 6657 AN: 248850 AF XY: 0.0265

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.0286

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0278

GnomAD4 exome AF: 0.0301 AC: 44029 AN: 1461530 Hom.: 823 Cov.: 158 AF XY: 0.0295 AC XY: 21434 AN XY: 727048

African (AFR) AF: 0.0118 AC: 396 AN: 33478

American (AMR) AF: 0.00570 AC: 255 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 761 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00952 AC: 821 AN: 86256

European-Finnish (FIN) AF: 0.0725 AC: 3864 AN: 53300

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

European-Non Finnish (NFE) AF: 0.0326 AC: 36249 AN: 1111812

Other (OTH) AF: 0.0274 AC: 1656 AN: 60366

GnomAD4 genome AF: 0.0251 AC: 3720 AN: 148368 Hom.: 47 Cov.: 31 AF XY: 0.0255 AC XY: 1844 AN XY: 72440

African (AFR) AF: 0.0135 AC: 537 AN: 39814

American (AMR) AF: 0.00740 AC: 111 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 98 AN: 3434

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4916

South Asian (SAS) AF: 0.00816 AC: 38 AN: 4656

European-Finnish (FIN) AF: 0.0687 AC: 703 AN: 10232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0326 AC: 2184 AN: 67088

Other (OTH) AF: 0.0229 AC: 47 AN: 2056

Alfa AF: 0.0309 Hom.: 16

Bravo AF: 0.0199

ClinVar

ClinVar submissions

Significance: Likely 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	-1.0
CADD	Benign	0.74
DANN	Benign	0.49
PhyloP100		-8.9
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs202088302;

hg19: chr11-1271784;