rs117736426

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002458.3(MUC5B):c.7829C>G(p.Thr2610Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,610,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.029 ( 1 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.172

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:

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

MUC5B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00386253).

BP6

Variant 11-1244709-C-G is Benign according to our data. Variant chr11-1244709-C-G is described in ClinVar as [Benign]. Clinvar id is 403144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2830/150888) while in subpopulation NFE AF= 0.0244 (1644/67278). AF 95% confidence interval is 0.0235. There are 0 homozygotes in gnomad4. There are 1422 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2830 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.7829C>G	p.Thr2610Ser	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-2071G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.7829C>G	p.Thr2610Ser	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-2071G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2831

AN:

150770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00539

Gnomad ASJ

AF:

0.0215

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00562

Gnomad FIN

AF:

0.0492

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0160

GnomAD3 exomes

AF:

0.0229

AC:

5665

AN:

247676

Hom.:

AF XY:

0.0228

AC XY:

3071

AN XY:

134466

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00747

Gnomad FIN exome

AF:

0.0697

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0290

AC:

42363

AN:

1459118

Hom.:

Cov.:

151

AF XY:

0.0284

AC XY:

20612

AN XY:

725838

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.00553

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00882

Gnomad4 FIN exome

AF:

0.0673

Gnomad4 NFE exome

AF:

0.0316

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0188

AC:

2830

AN:

150888

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1422

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.00538

Gnomad4 ASJ

AF:

0.0215

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00542

Gnomad4 FIN

AF:

0.0492

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0158

Alfa

AF:

0.0151

Hom.:

ESP6500AA

AF:

0.0160

AC:

ESP6500EA

AF:

0.0325

AC:

273

ExAC

AF:

0.0273

AC:

3302

ClinVar

Significance: 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: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.0

DANN

Benign

0.63

DEOGEN2

Benign

0.025

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.72

REVEL

Benign

0.014

Sift

Pathogenic

0.0

Vest4

0.050

ClinPred

0.011

GERP RS

0.40

Varity_R

0.10

gMVP

0.14

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