Variant 9-128504933-C-G 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_001003722.2(GLE1):c.99+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,455,298 control chromosomes in the GnomAD database, including 3,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 306 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2937 hom. )

Consequence

GLE1
NM_001003722.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.160

Variant links:

Genes affected

GLE1 (HGNC:4315): (GLE1 RNA export mediator) This gene encodes a predicted 75-kDa polypeptide with high sequence and structure homology to yeast Gle1p, which is nuclear protein with a leucine-rich nuclear export sequence essential for poly(A)+RNA export. Inhibition of human GLE1L by microinjection of antibodies against GLE1L in HeLa cells resulted in inhibition of poly(A)+RNA export. Immunoflourescence studies show that GLE1L is localized at the nuclear pore complexes. This localization suggests that GLE1L may act at a terminal step in the export of mature RNA messages to the cytoplasm. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GLE1 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=-0.79).

BP6

Variant 9-128504933-C-G is Benign according to our data. Variant chr9-128504933-C-G is described in ClinVar as [Benign]. Clinvar id is 1185280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLE1	NM_001003722.2 linkuse as main transcript	c.99+29C>G		intron_variant		ENST00000309971.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLE1	ENST00000309971.9 linkuse as main transcript	c.99+29C>G		intron_variant		1	NM_001003722.2	P1	Q53GS7-1

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7572

AN:

152202

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0913

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0875

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0441

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0780

AC:

19380

AN:

248556

Hom.:

1071

AF XY:

0.0779

AC XY:

10506

AN XY:

134896

show subpopulations

Gnomad AFR exome

AF:

0.00872

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0817

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0680

GnomAD4 exome

AF:

0.0556

AC:

72434

AN:

1302978

Hom.:

2937

Cov.:

AF XY:

0.0575

AC XY:

37751

AN XY:

656168

show subpopulations

Gnomad4 AFR exome

AF:

0.00771

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.0592

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0808

Gnomad4 NFE exome

AF:

0.0420

Gnomad4 OTH exome

AF:

0.0598

GnomAD4 genome

AF:

0.0497

AC:

7568

AN:

152320

Hom.:

306

Cov.:

AF XY:

0.0548

AC XY:

4080

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0909

Gnomad4 ASJ

AF:

0.0602

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.0875

Gnomad4 NFE

AF:

0.0441

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0485

Hom.:

Bravo

AF:

0.0489

Asia WGS

AF:

0.127

AC:

440

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lethal arthrogryposis-anterior horn cell disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Lethal congenital contracture syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.6

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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