dbSNP rs202088302: MUC5B:p.Thr4558Thr (chr11-1250554-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002458.3(MUC5B):c.13674T>C(p.Thr4558Thr) 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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.90

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 3720 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.13674T>C	p.Thr4558Thr	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.13674T>C	p.Thr4558Thr	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3721

AN:

148244

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0255

AC XY:

1844

AN XY:

72440

show subpopulations

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.:

Bravo

AF:

0.0199

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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

-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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over