rs12418291

chr11-1250278-G-Achr11-1250278-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002458.3(MUC5B):c.13398G>A(p.Thr4466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,611,090 control chromosomes in the GnomAD database, including 80,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7153 hom., cov: 30)
  • Exomes 𝑓: 0.31 (73293 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.38

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-1250278-G-A is Benign according to our data. Variant chr11-1250278-G-A is described in ClinVar as [Benign]. Clinvar id is 403176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.13398G>A	p.Thr4466=	synonymous_variant	31/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.13398G>A	p.Thr4466=	synonymous_variant	31/49	5	NM_002458.3	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44186 AN: 149938 Hom.: 7138 Cov.: 30

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.320 AC: 78854 AN: 246290 Hom.: 13710 AF XY: 0.319 AC XY: 42790 AN XY: 134154

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.609

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.312 AC: 455742 AN: 1461032 Hom.: 73293 Cov.: 120 AF XY: 0.310 AC XY: 225537 AN XY: 726768

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.295 AC: 44221 AN: 150058 Hom.: 7153 Cov.: 30 AF XY: 0.296 AC XY: 21642 AN XY: 73200

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.320

Alfa AF: 0.293 Hom.: 1170

Bravo AF: 0.294

EpiCase AF: 0.309

EpiControl AF: 0.313

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.3
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs12418291; hg19: chr11-1271508; COSMIC: COSV71593934; COSMIC: COSV71593934;