rs4963059

Variant names:

• chr11-1251628-C-T
• rs4963059
• NM_002458.3:c.14748C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1251628-C-T
• chr11-1251628-C-A
• chr11-1251628-C-G

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.14748C>T​(p.Phe4916Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,612,710 control chromosomes in the GnomAD database, including 79,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6937 hom., cov: 33)
  • Exomes 𝑓: 0.31 (72823 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01
• Publications: 22 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=-0.83).
• BP6: Variant 11-1251628-C-T is Benign according to our data. Variant chr11-1251628-C-T is described in ClinVar as Benign. ClinVar VariationId is 403180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 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.14748C>T	p.Phe4916Phe	synonymous	Exon 31 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.14748C>T	p.Phe4916Phe	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44394 AN: 152092 Hom.: 6923 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.320 AC: 79050 AN: 247284 AF XY: 0.318

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.311 AC: 454507 AN: 1460500 Hom.: 72823 Cov.: 59 AF XY: 0.309 AC XY: 224794 AN XY: 726518

African (AFR) AF: 0.208 AC: 6958 AN: 33476

American (AMR) AF: 0.308 AC: 13748 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 7227 AN: 26124

East Asian (EAS) AF: 0.595 AC: 23600 AN: 39690

South Asian (SAS) AF: 0.275 AC: 23715 AN: 86246

European-Finnish (FIN) AF: 0.282 AC: 14829 AN: 52536

Middle Eastern (MID) AF: 0.286 AC: 1650 AN: 5764

European-Non Finnish (NFE) AF: 0.309 AC: 343961 AN: 1111656

Other (OTH) AF: 0.312 AC: 18819 AN: 60350

GnomAD4 genome AF: 0.292 AC: 44433 AN: 152210 Hom.: 6937 Cov.: 33 AF XY: 0.293 AC XY: 21816 AN XY: 74422

African (AFR) AF: 0.215 AC: 8929 AN: 41542

American (AMR) AF: 0.332 AC: 5074 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 980 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3095 AN: 5170

South Asian (SAS) AF: 0.283 AC: 1366 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2965 AN: 10604

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20949 AN: 67988

Other (OTH) AF: 0.318 AC: 671 AN: 2108

Alfa AF: 0.304 Hom.: 26914

Bravo AF: 0.293

Asia WGS AF: 0.482 AC: 1673 AN: 3478

EpiCase AF: 0.309

EpiControl AF: 0.312

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	-0.83
CADD	Benign	1.5
DANN	Benign	0.73
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4963059; hg19: chr11-1272858; COSMIC: COSV101500051; COSMIC: COSV101500051;