rs41306469

chr9-128527566-G-Achr9-128527566-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.129

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLE1	NM_001003722.2	c.1312+41G>A		intron_variant		ENST00000309971.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLE1	ENST00000309971.9	c.1312+41G>A		intron_variant		1	NM_001003722.2	P1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2418 AN: 152142 Hom.: 25 Cov.: 31

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.: 18 AF XY: 0.0114 AC XY: 1532 AN XY: 134674

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.: 89 Cov.: 14 AF XY: 0.0109 AC XY: 5768 AN XY: 529070

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.: 25 Cov.: 31 AF XY: 0.0152 AC XY: 1135 AN XY: 74454

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.: 3

Bravo AF: 0.0173

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 15, 2019

- -

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

Other links and lift over

dbSNP: rs41306469; hg19: chr9-131289845;