rs869455

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001003722.2(GLE1):c.1242+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,397,660 control chromosomes in the GnomAD database, including 34,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3626 hom., cov: 31)

Exomes 𝑓: 0.22 ( 30429 hom. )

Consequence

GLE1
NM_001003722.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.90

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

lethal arthrogryposis-anterior horn cell disease syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
lethal congenital contracture syndrome 1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

GLE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-128527321-G-T is Benign according to our data. Variant chr9-128527321-G-T is described in ClinVar as Benign. ClinVar VariationId is 256856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003722.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLE1	NM_001003722.2	MANE Select	c.1242+30G>T	intron	N/A	NP_001003722.1	Q53GS7-1
GLE1	NM_001411013.1		c.1242+30G>T	intron	N/A	NP_001397942.1	A0A804HJ70
GLE1	NM_001499.2		c.1242+30G>T	intron	N/A	NP_001490.1	B3KMG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLE1	ENST00000309971.9	TSL:1 MANE Select	c.1242+30G>T	intron	N/A	ENSP00000308622.5	Q53GS7-1
GLE1	ENST00000372770.4	TSL:1	c.1242+30G>T	intron	N/A	ENSP00000361856.4	Q53GS7-2
GLE1	ENST00000898507.1		c.1242+30G>T	intron	N/A	ENSP00000568566.1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32274

AN:

151928

Hom.:

3617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.234

AC:

58237

AN:

249034

AF XY:

0.237

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.216

AC:

268592

AN:

1245614

Hom.:

30429

Cov.:

AF XY:

0.218

AC XY:

137675

AN XY:

630574

show subpopulations

African (AFR)

AF:

0.211

AC:

6205

AN:

29400

American (AMR)

AF:

0.224

AC:

9879

AN:

44148

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

3757

AN:

24724

East Asian (EAS)

AF:

0.395

AC:

15280

AN:

38732

South Asian (SAS)

AF:

0.303

AC:

24799

AN:

81966

European-Finnish (FIN)

AF:

0.235

AC:

12500

AN:

53248

Middle Eastern (MID)

AF:

0.242

AC:

1296

AN:

5356

European-Non Finnish (NFE)

AF:

0.200

AC:

183255

AN:

914672

Other (OTH)

AF:

0.218

AC:

11621

AN:

53368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10589

21179

31768

42358

52947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6066

12132

18198

24264

30330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.212

AC:

32294

AN:

152046

Hom.:

3626

Cov.:

AF XY:

0.218

AC XY:

16239

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.203

AC:

8430

AN:

41468

American (AMR)

AF:

0.211

AC:

3218

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

501

AN:

3468

East Asian (EAS)

AF:

0.392

AC:

2019

AN:

5152

South Asian (SAS)

AF:

0.324

AC:

1561

AN:

4820

European-Finnish (FIN)

AF:

0.251

AC:

2659

AN:

10586

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13270

AN:

67982

Other (OTH)

AF:

0.204

AC:

431

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1260

2520

3779

5039

6299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.184

Hom.:

2171

Bravo

AF:

0.212

Asia WGS

AF:

0.346

AC:

1202

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Lethal arthrogryposis-anterior horn cell disease syndrome (1)

Lethal congenital contracture syndrome 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.2

(source)

DANN

Benign

0.70

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over