rs202088302

chr11-1250554-T-Cchr11-1250554-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002458.3(MUC5B):c.13674T>C(p.Thr4558=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,609,898 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (47 hom., cov: 31)
  • Exomes 𝑓: 0.030 (823 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.90

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-1250554-T-C is Benign according to our data. Variant chr11-1250554-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.9 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3720/148368) while in subpopulation NFE AF= 0.0326 (2184/67088). AF 95% confidence interval is 0.0314. There are 47 homozygotes in gnomad4. There are 1844 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 3721 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.13674T>C	p.Thr4558=	synonymous_variant	31/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.13674T>C	p.Thr4558=	synonymous_variant	31/49	5	NM_002458.3	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3721 AN: 148244 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00741

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00816

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0232

GnomAD3 exomes AF: 0.0268 AC: 6657 AN: 248850 Hom.: 146 AF XY: 0.0265 AC XY: 3584 AN XY: 135112

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.0286

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00948

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0278

GnomAD4 exome AF: 0.0301 AC: 44029 AN: 1461530 Hom.: 823 Cov.: 158 AF XY: 0.0295 AC XY: 21434 AN XY: 727048

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00952

Gnomad4 FIN exome AF: 0.0725

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0251 AC: 3720 AN: 148368 Hom.: 47 Cov.: 31 AF XY: 0.0255 AC XY: 1844 AN XY: 72440

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.00740

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.00816

Gnomad4 FIN AF: 0.0687

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0229

Alfa AF: 0.0309 Hom.: 16

Bravo AF: 0.0199

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.74
Dann	Benign	0.49

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: rs202088302; hg19: chr11-1271784;