rs11605113

chr11-1243132-A-G

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.6252A>G(p.Thr2084=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,606,930 control chromosomes in the GnomAD database, including 80,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6796 hom., cov: 27)
  • Exomes 𝑓: 0.31 (74033 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.70

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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-1243132-A-G is Benign according to our data. Variant chr11-1243132-A-G is described in ClinVar as [Benign]. Clinvar id is 403135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.6252A>G	p.Thr2084=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-494T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.6252A>G	p.Thr2084=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-494T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 43564 AN: 149072 Hom.: 6784 Cov.: 27

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.327 AC: 79208 AN: 242464 Hom.: 14410 AF XY: 0.325 AC XY: 42843 AN XY: 131812

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.609

Gnomad SAS exome AF: 0.284

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.313 AC: 456536 AN: 1457736 Hom.: 74033 Cov.: 116 AF XY: 0.312 AC XY: 225913 AN XY: 725118

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.292 AC: 43597 AN: 149194 Hom.: 6796 Cov.: 27 AF XY: 0.293 AC XY: 21341 AN XY: 72726

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.319

Alfa AF: 0.294 Hom.: 1173

Bravo AF: 0.295

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

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.36

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: rs11605113; hg19: chr11-1264362; COSMIC: COSV71592180; COSMIC: COSV71592180;