Variant 11-1227154-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_StrongBS1BS2

The NM_002458.3(MUC5B):c.576+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,606,824 control chromosomes in the GnomAD database, including 894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 58 hom., cov: 35)

Exomes 𝑓: 0.030 ( 836 hom. )

Consequence

MUC5B
NM_002458.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0320

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 (HGNC:):

MUC5B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 11-1227154-G-T is Benign according to our data. Variant chr11-1227154-G-T is described in ClinVar as [Benign]. Clinvar id is 163994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1227154-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.023 (3501/152350) while in subpopulation NFE AF= 0.033 (2246/68018). AF 95% confidence interval is 0.0319. There are 58 homozygotes in gnomad4. There are 1747 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3501 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.576+9G>T		intron_variant		ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.576+9G>T		intron_variant		5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 linkuse as main transcript	n.634+9G>T		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3501

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00559

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0262

AC:

6372

AN:

243238

Hom.:

131

AF XY:

0.0260

AC XY:

3455

AN XY:

132812

show subpopulations

Gnomad AFR exome

AF:

0.00617

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00963

Gnomad FIN exome

AF:

0.0750

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0301

AC:

43732

AN:

1454474

Hom.:

836

Cov.:

AF XY:

0.0294

AC XY:

21256

AN XY:

722624

show subpopulations

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.00529

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00988

Gnomad4 FIN exome

AF:

0.0728

Gnomad4 NFE exome

AF:

0.0328

Gnomad4 OTH exome

AF:

0.0272

GnomAD4 genome

AF:

0.0230

AC:

3501

AN:

152350

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

1747

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00558

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.0330

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00260

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

Feb 21, 2013

576+9G>T in intron 5 of MUC5B: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 3.2% (268/8278) of European American chromosomes f rom a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS; dbSNP rs56394097). -

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

-0.73

CADD

Benign

7.2

DANN

Benign

0.69

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