11-1234543-C-T

Variant names:

• chr11-1234543-C-T
• rs7116614
• NM_002458.3:c.2493C>T

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.2493C>T​(p.Cys831Cys) 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 1,579,296 control chromosomes in the GnomAD database, including 78,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6980 hom., cov: 30)
  • Exomes 𝑓: 0.31 (71327 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.659

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=-0.62).
• BP6: Variant 11-1234543-C-T is Benign according to our data. Variant chr11-1234543-C-T is described in ClinVar as [Benign]. Clinvar id is 163998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.659 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.2493C>T	p.Cys831Cys	synonymous_variant	Exon 21 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.2493C>T	p.Cys831Cys	synonymous_variant	Exon 21 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.2551C>T		non_coding_transcript_exon_variant	Exon 21 of 26	1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44525 AN: 151726 Hom.: 6966 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.311 AC: 60954 AN: 195868 Hom.: 10186 AF XY: 0.309 AC XY: 32569 AN XY: 105440

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.312 AC: 444827 AN: 1427450 Hom.: 71327 Cov.: 49 AF XY: 0.310 AC XY: 218954 AN XY: 706700

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.293 AC: 44560 AN: 151846 Hom.: 6980 Cov.: 30 AF XY: 0.295 AC XY: 21881 AN XY: 74202

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.320

Alfa AF: 0.298 Hom.: 3181

Bravo AF: 0.295

Asia WGS AF: 0.481 AC: 1670 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cys831Cys in exon 21 of MUC5B: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 28.9% (2440/8444) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7116614). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.2
DANN	Benign	0.67

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: rs7116614; hg19: chr11-1255773; COSMIC: COSV71593296; COSMIC: COSV71593296;