Variant 11-1219991-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 ENST00000654177.1(ENSG00000286275):n.661G>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,220 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (★★).

Frequency

Genomes: 𝑓 0.079 ( 596 hom., cov: 33)

Consequence

ENSG00000286275
ENST00000654177.1 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Benign; risk factor criteria provided, multiple submitters, no conflicts U:1B:1O:3

Conservation

PhyloP100: 0.183

Variant links:

Genes affected

ENSG00000286275 (HGNC:):

ENSG00000286275 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=-0.68).

BP6

Variant 11-1219991-G-T is Benign according to our data. Variant chr11-1219991-G-T is described in ClinVar as [Benign, risk_factor]. Clinvar id is 30126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286275	ENST00000654177.1 link	n.661G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0794

AC:

12074

AN:

152102

Hom.:

595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0851

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00694

Gnomad SAS

AF:

0.0838

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0861

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0793

AC:

12074

AN:

152220

Hom.:

596

Cov.:

AF XY:

0.0803

AC XY:

5978

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0206

Gnomad4 AMR

AF:

0.0850

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.00695

Gnomad4 SAS

AF:

0.0849

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0843

Alfa

AF:

0.0264

Hom.:

Bravo

AF:

0.0747

ClinVar

Significance: Benign; risk factor

Submissions summary: Uncertain:1Benign:1Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Susceptibility to coronavirus disease (COVID-19) severity and mortality due to low plasma levels of MUC5B

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 13, 2022

Differences in plasma levels of MUC5B according to genotypes -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

MUC5B: BS1, BS2 -

Antisynthetase syndrome

Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 15, 2024

Usual Interstitial Pneumonia was observed in the patients -

Interstitial lung disease 2

Other:1

risk factor, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 04, 2020

MUC5B c.-3133G>T has been associated with increased risk for idiopathic pulmonary fibrosis. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (16.2%, Genome Aggregation Database (gnomAD); rs35705950) and is present in ClinVar (ID: 30126). Several studies have reported an odds ratios between 3.7-8.3 for developing pulmonary fibrosis in heterozygous individuals (OR=6.3 [95% CI 4.6-8.7] Borie 2013, OR=6.3 [95% CI 3.1-12.7] Hunninghake 2013, OR=8.3 [95% CI 5.8-11.9] Seibold 2013, OR=4.9 [95% CI 3.42-7.03] Stock 2013, OR=5.72 [95% CI 4.7-7.1] Lee 2015, OR=6.2 [95% CI 5.14-7.48] Zhu 2015) and odds ratios between 11.3-21.7 for developing pulmonary fibrosis in homozygous individuals (OR=21.7 [95% CI 104-45.3] Borie 2013, OR=12.98 [95% CI 7.97-21.12] Lee 2015, OR=11.29 [95% CI 5.69-22.40] Zhu 2015). MUC5B c.-3133G>T is a promoter variant that results in increased MUC5B expression (Seibold 2011, Nakano 2016, Kaur 2017). In summary, this variant is an established risk factor for idiopathic pulmonary fibrosis. -

Pulmonary fibrosis, idiopathic, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 06, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.3

DANN

Benign

0.69

Splicing

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