chr11-1242702-C-G

Position:

chr11-1242702-C-G

Variant summary

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

The NM_002458.3(MUC5B):c.5822C>G(p.Thr1941Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,613,430 control chromosomes in the GnomAD database, including 10 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 ( 6 hom., cov: 32)

Exomes 𝑓: 0.030 ( 4 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.245

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=0.0031417608).

BP6

Variant 11-1242702-C-G is Benign according to our data. Variant chr11-1242702-C-G is described in ClinVar as [Benign]. Clinvar id is 403132.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 = 0.0246 (3741/151826) while in subpopulation NFE AF= 0.0323 (2195/67856). AF 95% confidence interval is 0.0312. There are 6 homozygotes in gnomad4. There are 1865 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3741 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.5822C>G	p.Thr1941Ser	missense_variant	31/49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.57-64G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.5822C>G	p.Thr1941Ser	missense_variant	31/49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.57-64G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3742

AN:

151708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00748

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00811

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.0262

AC:

6524

AN:

249252

Hom.:

AF XY:

0.0259

AC XY:

3501

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00925

Gnomad FIN exome

AF:

0.0720

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0296

AC:

43274

AN:

1461604

Hom.:

Cov.:

107

AF XY:

0.0290

AC XY:

21078

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00568

Gnomad4 ASJ exome

AF:

0.0289

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00934

Gnomad4 FIN exome

AF:

0.0700

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0246

AC:

3741

AN:

151826

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1865

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00747

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00812

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0303

Hom.:

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.0131

AC:

ESP6500EA

AF:

0.0315

AC:

268

ExAC

AF:

0.0273

AC:

3306

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

DANN

Benign

0.67

DEOGEN2

Benign

0.031

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.67

REVEL

Benign

0.024

Sift

Benign

0.037

Vest4

0.027

ClinPred

0.00013

GERP RS

1.2

Varity_R

0.042

gMVP

0.26

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