rs2334757

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002458.3(MUC5B):c.10821A>C(p.Ala3607Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,315,020 control chromosomes in the GnomAD database, including 96,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8667 hom., cov: 26)

Exomes 𝑓: 0.24 ( 88289 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.66

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 11-1247701-A-C is Benign according to our data. Variant chr11-1247701-A-C is described in ClinVar as [Benign]. Clinvar id is 403165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.10821A>C	p.Ala3607Ala	synonymous_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2	Q9HC84
MUC5B-AS1	NR_157183.1 link	n.56+1920T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.10821A>C	p.Ala3607Ala	synonymous_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B-AS1	ENST00000532061.2 link	n.56+1920T>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

47027

AN:

140838

Hom.:

8652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.378

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.282

AC:

54820

AN:

194570

Hom.:

12030

AF XY:

0.279

AC XY:

29514

AN XY:

105600

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.547

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.236

AC:

276554

AN:

1174056

Hom.:

88289

Cov.:

110

AF XY:

0.238

AC XY:

139730

AN XY:

587684

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.334

AC:

47088

AN:

140964

Hom.:

8667

Cov.:

AF XY:

0.331

AC XY:

22683

AN XY:

68496

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.577

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.244

Hom.:

952

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

DANN

Benign

0.43

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