rs2037089

Variant names:

• chr11-1241677-T-C
• rs2037089
• NM_002458.3:c.4797T>C

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.4797T>C​(p.Ser1599Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,611,266 control chromosomes in the GnomAD database, including 34,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4130 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30789 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.46
• Publications: 20 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=-0.93).
• BP6: Variant 11-1241677-T-C is Benign according to our data. Variant chr11-1241677-T-C is described in ClinVar as Benign. ClinVar VariationId is 196682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.4797T>C	p.Ser1599Ser	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.4797T>C	p.Ser1599Ser	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34593 AN: 151736 Hom.: 4112 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.216

GnomAD2 exomes AF: 0.220 AC: 53472 AN: 242542 AF XY: 0.216

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.0600

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.201 AC: 293564 AN: 1459412 Hom.: 30789 Cov.: 50 AF XY: 0.202 AC XY: 146509 AN XY: 725938

African (AFR) AF: 0.284 AC: 9506 AN: 33450

American (AMR) AF: 0.308 AC: 13654 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6335 AN: 26124

East Asian (EAS) AF: 0.110 AC: 4371 AN: 39656

South Asian (SAS) AF: 0.225 AC: 19407 AN: 86150

European-Finnish (FIN) AF: 0.291 AC: 15187 AN: 52250

Middle Eastern (MID) AF: 0.233 AC: 1345 AN: 5766

European-Non Finnish (NFE) AF: 0.190 AC: 211611 AN: 1111314

Other (OTH) AF: 0.201 AC: 12148 AN: 60316

GnomAD4 genome AF: 0.228 AC: 34641 AN: 151854 Hom.: 4130 Cov.: 32 AF XY: 0.233 AC XY: 17259 AN XY: 74218

African (AFR) AF: 0.279 AC: 11566 AN: 41400

American (AMR) AF: 0.253 AC: 3858 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3464

East Asian (EAS) AF: 0.0693 AC: 357 AN: 5152

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4812

European-Finnish (FIN) AF: 0.305 AC: 3220 AN: 10544

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13082 AN: 67894

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.210 Hom.: 1736

Bravo AF: 0.228

Asia WGS AF: 0.136 AC: 475 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 22, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:2

Jun 09, 2021

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.53
PhyloP100		-1.5
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: rs2037089; hg19: chr11-1262907; COSMIC: COSV71594279; COSMIC: COSV71594279;