rs908229

Variant names:

• chr11-1232712-T-C
• rs908229
• NM_002458.3:c.2007T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.2007T>C​(p.Tyr669Tyr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.577
• Publications: 14 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 -20 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 VariationId is 163997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 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.2007T>C	p.Tyr669Tyr	synonymous	Exon 17 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.2007T>C	p.Tyr669Tyr	synonymous	Exon 17 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.2065T>C		non_coding_transcript_exon	Exon 17 of 26

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

GnomAD2 exomes AF: 0.628 AC: 141750 AN: 225866 AF XY: 0.626

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.673

Gnomad ASJ exome AF: 0.640

Gnomad EAS exome AF: 0.697

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.605

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

African (AFR) AF: 0.492 AC: 16327 AN: 33214

American (AMR) AF: 0.614 AC: 26121 AN: 42560

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 13936 AN: 25808

East Asian (EAS) AF: 0.701 AC: 27310 AN: 38940

South Asian (SAS) AF: 0.505 AC: 42378 AN: 83912

European-Finnish (FIN) AF: 0.576 AC: 29136 AN: 50626

Middle Eastern (MID) AF: 0.520 AC: 2989 AN: 5752

European-Non Finnish (NFE) AF: 0.501 AC: 553813 AN: 1104702

Other (OTH) AF: 0.516 AC: 30825 AN: 59752

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

African (AFR) AF: 0.495 AC: 20547 AN: 41512

American (AMR) AF: 0.589 AC: 8999 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1899 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3418 AN: 5164

South Asian (SAS) AF: 0.506 AC: 2444 AN: 4826

European-Finnish (FIN) AF: 0.588 AC: 6220 AN: 10580

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34203 AN: 67980

Other (OTH) AF: 0.536 AC: 1133 AN: 2114

Alfa AF: 0.556 Hom.: 3710

Bravo AF: 0.523

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.43
DANN	Benign	0.18
PhyloP100		-0.58
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: rs908229; hg19: chr11-1253942; COSMIC: COSV71590016; COSMIC: COSV71590016;