rs56025628

chr11-1258382-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002458.3(MUC5B):c.16593+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,611,084 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (61 hom., cov: 32)
  • Exomes 𝑓: 0.030 (831 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-1258382-G-C is Benign according to our data. Variant chr11-1258382-G-C is described in ClinVar as [Benign]. Clinvar id is 226736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3802/152304) while in subpopulation NFE AF= 0.0327 (2227/68008). AF 95% confidence interval is 0.0316. There are 61 homozygotes in gnomad4. There are 1887 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 3803 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.16593+15G>C		intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.16593+15G>C		intron_variant		5	NM_002458.3	P1
MUC5B	ENST00000526859.1	c.228+15G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3803 AN: 152186 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0260 AC: 6379 AN: 245256 Hom.: 126 AF XY: 0.0256 AC XY: 3424 AN XY: 133552

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.00500

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00929

Gnomad FIN exome AF: 0.0728

Gnomad NFE exome AF: 0.0336

Gnomad OTH exome AF: 0.0275

GnomAD4 exome AF: 0.0300 AC: 43718 AN: 1458780 Hom.: 831 Cov.: 34 AF XY: 0.0293 AC XY: 21262 AN XY: 725560

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.00547

Gnomad4 ASJ exome AF: 0.0290

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00944

Gnomad4 FIN exome AF: 0.0722

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0250 AC: 3802 AN: 152304 Hom.: 61 Cov.: 32 AF XY: 0.0253 AC XY: 1887 AN XY: 74472

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00807

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0308 Hom.: 15

Bravo AF: 0.0198

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 13, 2015

c.16593+15G>C in 43 of MUC5B: This variant is not expected to have clinical sign ificance because it has been identified in 4% (2330/62894) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs56025628). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.11
Dann	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs56025628; hg19: chr11-1279612;