rs2857476

Variant names:

• chr11-1259904-T-C
• rs2857476
• NM_002458.3:c.16801-59T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.16801-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,611,726 control chromosomes in the GnomAD database, including 221,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22765 hom., cov: 34)
  • Exomes 𝑓: 0.52 (198605 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.57
• Publications: 25 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-1259904-T-C is Benign according to our data. Variant chr11-1259904-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.16801-59T>C		intron	N/A	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.16801-59T>C		intron	N/A	ENSP00000436812.1
	MUC5B	ENST00000526859.1	TSL:3	c.435+62T>C		intron	N/A	ENSP00000434539.1
	MUC5B	ENST00000527802.1	TSL:3	n.321-59T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82711 AN: 151934 Hom.: 22730 Cov.: 34

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.519 AC: 758155 AN: 1459676 Hom.: 198605 Cov.: 49 AF XY: 0.518 AC XY: 376202 AN XY: 725958

African (AFR) AF: 0.561 AC: 18785 AN: 33464

American (AMR) AF: 0.619 AC: 27662 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 14000 AN: 26076

East Asian (EAS) AF: 0.725 AC: 28780 AN: 39682

South Asian (SAS) AF: 0.511 AC: 44056 AN: 86190

European-Finnish (FIN) AF: 0.582 AC: 30458 AN: 52368

Middle Eastern (MID) AF: 0.531 AC: 3058 AN: 5758

European-Non Finnish (NFE) AF: 0.504 AC: 559867 AN: 1111162

Other (OTH) AF: 0.522 AC: 31489 AN: 60298

GnomAD4 genome AF: 0.545 AC: 82798 AN: 152050 Hom.: 22765 Cov.: 34 AF XY: 0.550 AC XY: 40856 AN XY: 74326

African (AFR) AF: 0.565 AC: 23413 AN: 41448

American (AMR) AF: 0.593 AC: 9076 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1883 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3511 AN: 5168

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4824

European-Finnish (FIN) AF: 0.594 AC: 6294 AN: 10592

Middle Eastern (MID) AF: 0.510 AC: 148 AN: 290

European-Non Finnish (NFE) AF: 0.505 AC: 34338 AN: 67938

Other (OTH) AF: 0.548 AC: 1157 AN: 2110

Alfa AF: 0.522 Hom.: 55995

Bravo AF: 0.547

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.51
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2857476; hg19: chr11-1281134;