Variant chr9-128527566-G-A 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_001003722.2(GLE1):c.1312+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,176,596 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 25 hom., cov: 31)

Exomes 𝑓: 0.011 ( 89 hom. )

Consequence

GLE1
NM_001003722.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.129

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:

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=-0.86).

BP6

Variant 9-128527566-G-A is Benign according to our data. Variant chr9-128527566-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0159 (2417/152260) while in subpopulation AFR AF= 0.0259 (1075/41548). AF 95% confidence interval is 0.0246. There are 25 homozygotes in gnomad4. There are 1135 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLE1	NM_001003722.2 linkuse as main transcript	c.1312+41G>A		intron_variant		ENST00000309971.9	NP_001003722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLE1	ENST00000309971.9 linkuse as main transcript	c.1312+41G>A		intron_variant		1	NM_001003722.2	ENSP00000308622	P1	Q53GS7-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2418

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0117

AC:

2928

AN:

249250

Hom.:

AF XY:

0.0114

AC XY:

1532

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00983

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00682

Gnomad FIN exome

AF:

0.00908

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0111

AC:

11368

AN:

1024336

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

5768

AN XY:

529070

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.00690

Gnomad4 FIN exome

AF:

0.00889

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0159

AC:

2417

AN:

152260

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00811

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

DANN

Benign

0.47

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