rs56229218

Variant names:

• chr11-1255464-T-C
• rs56229218
• NM_002458.3:c.15972T>C

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.15972T>C​(p.Leu5324Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,537,202 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (64 hom., cov: 31)
  • Exomes 𝑓: 0.011 (349 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.64
• Publications: 5 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=-0.95).
• BP6: Variant 11-1255464-T-C is Benign according to our data. Variant chr11-1255464-T-C is described in ClinVar as Benign. ClinVar VariationId is 178795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3774/151982) while in subpopulation NFE AF = 0.0325 (2206/67880). AF 95% confidence interval is 0.0314. There are 64 homozygotes in GnomAd4. There are 1873 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.15972T>C	p.Leu5324Leu	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.15972T>C	p.Leu5324Leu	synonymous	Exon 37 of 49	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3775 AN: 151864 Hom.: 64 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00747

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.0124 AC: 2577 AN: 207460 AF XY: 0.0118

Gnomad AFR exome AF: 0.00979

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00668

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0466

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0128

GnomAD4 exome AF: 0.0106 AC: 14721 AN: 1385220 Hom.: 349 Cov.: 35 AF XY: 0.0109 AC XY: 7504 AN XY: 688922

African (AFR) AF: 0.00538 AC: 175 AN: 32542

American (AMR) AF: 0.00317 AC: 133 AN: 41972

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 407 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 38534

South Asian (SAS) AF: 0.00570 AC: 471 AN: 82596

European-Finnish (FIN) AF: 0.0653 AC: 3243 AN: 49654

Middle Eastern (MID) AF: 0.00262 AC: 15 AN: 5718

European-Non Finnish (NFE) AF: 0.00907 AC: 9536 AN: 1051256

Other (OTH) AF: 0.0128 AC: 741 AN: 57844

GnomAD4 genome AF: 0.0248 AC: 3774 AN: 151982 Hom.: 64 Cov.: 31 AF XY: 0.0252 AC XY: 1873 AN XY: 74310

African (AFR) AF: 0.0130 AC: 538 AN: 41468

American (AMR) AF: 0.00746 AC: 114 AN: 15290

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

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.00809 AC: 39 AN: 4822

European-Finnish (FIN) AF: 0.0689 AC: 730 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0325 AC: 2206 AN: 67880

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.0268 Hom.: 33

Bravo AF: 0.0198

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	-0.95
CADD	Benign	0.12
DANN	Benign	0.29
PhyloP100		-2.6
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

Other links and lift over

dbSNP: rs56229218; hg19: chr11-1276694;