rs2857476

Positions:

• chr11-1259904-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.16801-59T>C		intron_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.16801-59T>C		intron_variant		5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000526859.1	c.435+62T>C		intron_variant		3		ENSP00000434539.1
MUC5B	ENST00000527802.1	n.321-59T>C		intron_variant		3

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

Gnomad4 AFR exome AF: 0.561

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.522

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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.548

Alfa AF: 0.517 Hom.: 32393

Bravo AF: 0.547

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2857476; hg19: chr11-1281134;