NM_001003722.2:c.1647-44A>G

Variant names:

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.1647-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,573,116 control chromosomes in the GnomAD database, including 45,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6249 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39438 hom. )

Consequence

GLE1
NM_001003722.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.646

Publications

6 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:

ENSG00000228395 (HGNC:):

ENSG00000228395 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=-0.99).

BP6

Variant 9-128536311-A-G is Benign according to our data. Variant chr9-128536311-A-G is described in ClinVar as Benign. ClinVar VariationId is 256858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 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.1647-44A>G	intron	N/A	NP_001003722.1	Q53GS7-1
GLE1	NM_001411013.1		c.1674-44A>G	intron	N/A	NP_001397942.1	A0A804HJ70
GLE1	NM_001499.2		c.1647-44A>G	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.1647-44A>G	intron	N/A	ENSP00000308622.5	Q53GS7-1
GLE1	ENST00000372770.4	TSL:1	c.1647-44A>G	intron	N/A	ENSP00000361856.4	Q53GS7-2
GLE1	ENST00000898507.1		c.1704-44A>G	intron	N/A	ENSP00000568566.1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41279

AN:

151968

Hom.:

6239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.255

GnomAD2 exomes

AF:

0.267

AC:

66527

AN:

248878

AF XY:

0.264

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.226

AC:

320503

AN:

1421030

Hom.:

39438

Cov.:

AF XY:

0.227

AC XY:

161201

AN XY:

708586

show subpopulations

African (AFR)

AF:

0.386

AC:

12522

AN:

32446

American (AMR)

AF:

0.300

AC:

13231

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

4220

AN:

25396

East Asian (EAS)

AF:

0.475

AC:

18146

AN:

38186

South Asian (SAS)

AF:

0.314

AC:

26770

AN:

85228

European-Finnish (FIN)

AF:

0.235

AC:

12223

AN:

51916

Middle Eastern (MID)

AF:

0.254

AC:

1422

AN:

5608

European-Non Finnish (NFE)

AF:

0.202

AC:

218099

AN:

1079748

Other (OTH)

AF:

0.238

AC:

13870

AN:

58382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

12622

25244

37865

50487

63109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7832

15664

23496

31328

39160

<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:

0.272

AC:

41320

AN:

152086

Hom.:

6249

Cov.:

AF XY:

0.276

AC XY:

20527

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.376

AC:

15614

AN:

41514

American (AMR)

AF:

0.258

AC:

3938

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

561

AN:

3472

East Asian (EAS)

AF:

0.467

AC:

2407

AN:

5156

South Asian (SAS)

AF:

0.342

AC:

1647

AN:

4820

European-Finnish (FIN)

AF:

0.253

AC:

2680

AN:

10580

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13726

AN:

67966

Other (OTH)

AF:

0.255

AC:

537

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1512

3024

4536

6048

7560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.229

Hom.:

836

Bravo

AF:

0.280

Asia WGS

AF:

0.423

AC:

1470

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

-0.99

CADD

Benign

1.4

(source)

DANN

Benign

0.74

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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