rs908229

Positions:

• chr11-1232712-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002458.3(MUC5B):​c.2007T>C​(p.Tyr669=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,597,398 control chromosomes in the GnomAD database, including 213,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20978 hom., cov: 35)
  • Exomes 𝑓: 0.51 (192122 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.577

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-1232712-T-C is Benign according to our data. Variant chr11-1232712-T-C is described in ClinVar as [Benign]. Clinvar id is 163997.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.2007T>C	p.Tyr669=	synonymous_variant	17/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.2007T>C	p.Tyr669=	synonymous_variant	17/49	5	NM_002458.3	P1
MUC5B	ENST00000525715.5	n.2065T>C		non_coding_transcript_exon_variant	17/26	1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79434 AN: 152014 Hom.: 20955 Cov.: 35

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.514 AC: 742835 AN: 1445266 Hom.: 192122 Cov.: 69 AF XY: 0.513 AC XY: 367971 AN XY: 717384

Gnomad4 AFR exome AF: 0.492

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.523 AC: 79503 AN: 152132 Hom.: 20978 Cov.: 35 AF XY: 0.529 AC XY: 39318 AN XY: 74374

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.536

Alfa AF: 0.556 Hom.: 3710

Bravo AF: 0.523

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Tyr669Tyr in exon 17 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 40.0% (1720/4300) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs908229). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.43
DANN	Benign	0.18

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: rs908229; hg19: chr11-1253942; COSMIC: COSV71590016; COSMIC: COSV71590016;