Variant 11-1258382-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002458.3(MUC5B):c.16593+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,611,084 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 61 hom., cov: 32)

Exomes 𝑓: 0.030 ( 831 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.31

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-1258382-G-C is Benign according to our data. Variant chr11-1258382-G-C is described in ClinVar as [Benign]. Clinvar id is 226736.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 = 0.025 (3802/152304) while in subpopulation NFE AF= 0.0327 (2227/68008). AF 95% confidence interval is 0.0316. There are 61 homozygotes in gnomad4. There are 1887 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3802 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.16593+15G>C		intron_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.16593+15G>C		intron_variant		5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000526859.1 linkuse as main transcript	c.228+15G>C		intron_variant		3		ENSP00000434539

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3803

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0260

AC:

6379

AN:

245256

Hom.:

126

AF XY:

0.0256

AC XY:

3424

AN XY:

133552

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00929

Gnomad FIN exome

AF:

0.0728

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0300

AC:

43718

AN:

1458780

Hom.:

831

Cov.:

AF XY:

0.0293

AC XY:

21262

AN XY:

725560

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.00547

Gnomad4 ASJ exome

AF:

0.0290

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00944

Gnomad4 FIN exome

AF:

0.0722

Gnomad4 NFE exome

AF:

0.0325

Gnomad4 OTH exome

AF:

0.0273

GnomAD4 genome

AF:

0.0250

AC:

3802

AN:

152304

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

1887

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.0688

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0308

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00404

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

Apr 13, 2015

c.16593+15G>C in 43 of MUC5B: This variant is not expected to have clinical sign ificance because it has been identified in 4% (2330/62894) of European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs56025628). -

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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