rs55845452

Variant names:

• chr11-1256199-C-A
• rs55845452
• NM_002458.3:c.16110C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1256199-C-A
• chr11-1256199-C-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.16110C>A​(p.Pro5370Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 734,482 control chromosomes in the GnomAD database, including 412 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: 31)
  • Exomes 𝑓: 0.028 (349 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.21
• Publications: 3 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=-0.77).
• BP6: Variant 11-1256199-C-A is Benign according to our data. Variant chr11-1256199-C-A is described in ClinVar as Benign. ClinVar VariationId is 178797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.025 (3804/152218) while in subpopulation NFE AF = 0.0327 (2226/67980). AF 95% confidence interval is 0.0316. There are 63 homozygotes in GnomAd4. There are 1894 alleles in the male GnomAd4 subpopulation. Median coverage is 31. 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.16110C>A	p.Pro5370Pro	synonymous	Exon 38 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.16110C>A	p.Pro5370Pro	synonymous	Exon 38 of 49	ENSP00000436812.1	Q9HC84

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3805 AN: 152098 Hom.: 63 Cov.: 31

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.0256 AC: 4636 AN: 181320 AF XY: 0.0250

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.00537

Gnomad ASJ exome AF: 0.0279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0317

Gnomad OTH exome AF: 0.0263

GnomAD4 exome AF: 0.0278 AC: 16159 AN: 582264 Hom.: 349 Cov.: 0 AF XY: 0.0264 AC XY: 8332 AN XY: 315182

African (AFR) AF: 0.0125 AC: 202 AN: 16224

American (AMR) AF: 0.00538 AC: 201 AN: 37372

Ashkenazi Jewish (ASJ) AF: 0.0281 AC: 568 AN: 20242

East Asian (EAS) AF: 0.00 AC: 0 AN: 32882

South Asian (SAS) AF: 0.00972 AC: 621 AN: 63878

European-Finnish (FIN) AF: 0.0722 AC: 3527 AN: 48868

Middle Eastern (MID) AF: 0.00438 AC: 18 AN: 4112

European-Non Finnish (NFE) AF: 0.0312 AC: 10200 AN: 327214

Other (OTH) AF: 0.0261 AC: 822 AN: 31472

GnomAD4 genome AF: 0.0250 AC: 3804 AN: 152218 Hom.: 63 Cov.: 31 AF XY: 0.0255 AC XY: 1894 AN XY: 74418

African (AFR) AF: 0.0131 AC: 543 AN: 41534

American (AMR) AF: 0.00738 AC: 113 AN: 15304

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4826

European-Finnish (FIN) AF: 0.0692 AC: 735 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0327 AC: 2226 AN: 67980

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0294 Hom.: 35

Bravo AF: 0.0198

Asia WGS AF: 0.00404 AC: 14 AN: 3478

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	-0.77
CADD	Benign	0.028
DANN	Benign	0.70
PhyloP100		-4.2
Mutation Taster		=97/3	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: rs55845452; hg19: chr11-1277429;