Variant 11-1226967-G-T 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.462-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,517,360 control chromosomes in the GnomAD database, including 306,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 28803 hom., cov: 30)

Exomes 𝑓: 0.63 ( 277355 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.69

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=-0.76).

BP6

Variant 11-1226967-G-T is Benign according to our data. Variant chr11-1226967-G-T is described in ClinVar as [Benign]. Clinvar id is 1282609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.462-64G>T		intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.462-64G>T		intron_variant		5	NM_002458.3	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.520-64G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

92643

AN:

146742

Hom.:

28771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.590

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.635

GnomAD4 exome

AF:

0.634

AC:

869176

AN:

1370510

Hom.:

277355

Cov.:

AF XY:

0.632

AC XY:

428298

AN XY:

677586

show subpopulations

Gnomad4 AFR exome

AF:

0.628

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.583

Gnomad4 EAS exome

AF:

0.595

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.676

Gnomad4 NFE exome

AF:

0.634

Gnomad4 OTH exome

AF:

0.634

GnomAD4 genome

AF:

0.631

AC:

92721

AN:

146850

Hom.:

28803

Cov.:

AF XY:

0.635

AC XY:

45480

AN XY:

71676

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.709

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.572

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.622

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.609

Hom.:

2945

Asia WGS

AF:

0.566

AC:

1965

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0020

DANN

Benign

0.61

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