rs184215485

Variant names:

Variant summary

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

The NM_002458.3(MUC5B):c.9626G>A(p.Arg3209Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 150,046 control chromosomes in the GnomAD database, including 68 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 0.025 ( 68 hom., cov: 32)

Exomes 𝑓: 0.026 ( 907 hom. )

Failed GnomAD Quality Control

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.15

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=0.0038914084).

BP6

Variant 11-1246506-G-A is Benign according to our data. Variant chr11-1246506-G-A is described in ClinVar as [Benign]. Clinvar id is 403157.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 = 0.0253 (3799/150046) while in subpopulation NFE AF= 0.033 (2222/67358). AF 95% confidence interval is 0.0318. There are 68 homozygotes in gnomad4. There are 1875 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3799 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.9626G>A	p.Arg3209Lys	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+3115C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.9626G>A	p.Arg3209Lys	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+3115C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3800

AN:

149924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.00840

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000403

Gnomad SAS

AF:

0.00772

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0223

GnomAD3 exomes

AF:

0.00978

AC:

2370

AN:

242354

Hom.:

112

AF XY:

0.00905

AC XY:

1188

AN XY:

131334

show subpopulations

Gnomad AFR exome

AF:

0.00726

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00569

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0434

Gnomad NFE exome

AF:

0.00996

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0257

AC:

37187

AN:

1447650

Hom.:

907

Cov.:

126

AF XY:

0.0251

AC XY:

18060

AN XY:

720182

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00480

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00772

Gnomad4 FIN exome

AF:

0.0681

Gnomad4 NFE exome

AF:

0.0276

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0253

AC:

3799

AN:

150046

Hom.:

Cov.:

AF XY:

0.0256

AC XY:

1875

AN XY:

73240

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00839

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.000404

Gnomad4 SAS

AF:

0.00773

Gnomad4 FIN

AF:

0.0688

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0221

Alfa

AF:

0.0303

Hom.:

Bravo

AF:

0.0204

ExAC

AF:

0.0228

AC:

2770

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

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

DANN

Benign

0.36

DEOGEN2

Benign

0.016

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.23

REVEL

Benign

0.0030

Sift

Benign

0.93

Vest4

0.0030

ClinPred

0.0047

GERP RS

-1.8

Varity_R

0.040

gMVP

0.17

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