Variant rs56069229 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002458.3(MUC5B):c.1103-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,552,268 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

MUC5B
NM_002458.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008234

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.1103-11G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MUC5B	ENST00000529681.5 linkuse as main transcript	c.1103-11G>A	splice_polypyrimidine_tract_variant, intron_variant	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.1161-11G>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
MUC5B	ENST00000531082.1 linkuse as main transcript	n.373-11G>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

160586

Hom.:

AF XY:

0.000171

AC XY:

AN XY:

87594

show subpopulations

Gnomad AFR exome

AF:

0.000118

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000893

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000126

AC:

177

AN:

1400120

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

692160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000940

Gnomad4 AMR exome

AF:

0.0000797

Gnomad4 ASJ exome

AF:

0.00265

Gnomad4 EAS exome

AF:

0.0000550

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000792

Gnomad4 OTH exome

AF:

0.000274

GnomAD4 genome

AF:

0.000112

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000220

Hom.:

Bravo

AF:

0.000196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.0060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over