Variant 11-1242457-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002458.3(MUC5B):c.5577C>T(p.Asn1859=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,613,718 control chromosomes in the GnomAD database, including 2,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 179 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2084 hom. )

Consequence

MUC5B
NM_002458.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.59

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=-0.79).

BP6

Variant 11-1242457-C-T is Benign according to our data. Variant chr11-1242457-C-T is described in ClinVar as [Benign]. Clinvar id is 1230323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 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.5577C>T	p.Asn1859=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1 linkuse as main transcript	n.238G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.5577C>T	p.Asn1859=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2 linkuse as main transcript	n.238G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0391

AC:

5946

AN:

152010

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0526

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0408

AC:

10157

AN:

249190

Hom.:

347

AF XY:

0.0417

AC XY:

5635

AN XY:

135140

show subpopulations

Gnomad AFR exome

AF:

0.00740

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0482

AC:

70484

AN:

1461590

Hom.:

2084

Cov.:

AF XY:

0.0474

AC XY:

34498

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00657

Gnomad4 AMR exome

AF:

0.0173

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0530

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0391

AC:

5945

AN:

152128

Hom.:

179

Cov.:

AF XY:

0.0416

AC XY:

3095

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00959

Gnomad4 AMR

AF:

0.0270

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0158

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.0526

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0451

Hom.:

Bravo

AF:

0.0300

Asia WGS

AF:

0.00693

AC:

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	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.89

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