Variant rs12421917 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.1843+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,576,108 control chromosomes in the GnomAD database, including 133,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14181 hom., cov: 34)

Exomes 𝑓: 0.41 ( 119263 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0370

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=-0.7).

BP6

Variant 11-1232171-C-G is Benign according to our data. Variant chr11-1232171-C-G is described in ClinVar as [Benign]. Clinvar id is 163996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.1843+11C>G		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.1843+11C>G		intron_variant		5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.1901+11C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65066

AN:

151926

Hom.:

14150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.436

GnomAD3 exomes

AF:

0.438

AC:

94316

AN:

215126

Hom.:

20591

AF XY:

0.434

AC XY:

50126

AN XY:

115512

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.615

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.408

AC:

581270

AN:

1424066

Hom.:

119263

Cov.:

AF XY:

0.407

AC XY:

286260

AN XY:

703334

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.599

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.398

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.428

AC:

65149

AN:

152042

Hom.:

14181

Cov.:

AF XY:

0.430

AC XY:

31972

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.454

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.603

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.404

Hom.:

2383

Bravo

AF:

0.439

Asia WGS

AF:

0.552

AC:

1918

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

1843+11C>G in intron 15 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 42.7% (1750/4098) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs12421917). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.3

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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