NM_002458.3:c.2493C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.2493C>T	p.Cys831Cys	synonymous	Exon 21 of 49	NP_002449.2	Q9HC84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.2493C>T	p.Cys831Cys	synonymous	Exon 21 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.2551C>T		non_coding_transcript_exon	Exon 21 of 26

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

GnomAD2 exomes AF: 0.311 AC: 60954 AN: 195868 AF XY: 0.309

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 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

African (AFR) AF: 0.209 AC: 6848 AN: 32796

American (AMR) AF: 0.302 AC: 12118 AN: 40180

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7528 AN: 25432

East Asian (EAS) AF: 0.591 AC: 22256 AN: 37636

South Asian (SAS) AF: 0.279 AC: 22636 AN: 81216

European-Finnish (FIN) AF: 0.281 AC: 13998 AN: 49842

Middle Eastern (MID) AF: 0.286 AC: 1634 AN: 5710

European-Non Finnish (NFE) AF: 0.310 AC: 339233 AN: 1095512

Other (OTH) AF: 0.314 AC: 18576 AN: 59126

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

African (AFR) AF: 0.215 AC: 8920 AN: 41410

American (AMR) AF: 0.331 AC: 5060 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3087 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1391 AN: 4802

European-Finnish (FIN) AF: 0.281 AC: 2965 AN: 10564

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21003 AN: 67874

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.297 Hom.: 3207

Bravo AF: 0.295

Asia WGS AF: 0.481 AC: 1670 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		-0.66
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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