Genetic Variant GLE1:c.1312+41G>A (chr9-128527566-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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=-0.86).

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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR,AD gene

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.1312+41G>A	intron	N/A	NP_001003722.1	Q53GS7-1
GLE1	NM_001411013.1		c.1312+41G>A	intron	N/A	NP_001397942.1	A0A804HJ70
GLE1	NM_001499.2		c.1312+41G>A	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.1312+41G>A	intron	N/A	ENSP00000308622.5	Q53GS7-1
GLE1	ENST00000372770.4	TSL:1	c.1312+41G>A	intron	N/A	ENSP00000361856.4	Q53GS7-2
GLE1	ENST00000898507.1		c.1312+41G>A	intron	N/A	ENSP00000568566.1

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

GnomAD2 exomes

AF:

0.0117

AC:

2928

AN:

249250

AF XY:

0.0114

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 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

African (AFR)

AF:

0.0257

AC:

646

AN:

25118

American (AMR)

AF:

0.0103

AC:

454

AN:

44056

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

475

AN:

23392

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37698

South Asian (SAS)

AF:

0.00690

AC:

533

AN:

77268

European-Finnish (FIN)

AF:

0.00889

AC:

473

AN:

53230

Middle Eastern (MID)

AF:

0.0373

AC:

183

AN:

4902

European-Non Finnish (NFE)

AF:

0.0113

AC:

8059

AN:

712624

Other (OTH)

AF:

0.0118

AC:

544

AN:

46048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

611

1222

1833

2444

3055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<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:

0.0159

AC:

2417

AN:

152260

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0259

AC:

1075

AN:

41548

American (AMR)

AF:

0.0157

AC:

240

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00559

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00811

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

857

AN:

68014

Other (OTH)

AF:

0.0165

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

123

246

370

493

616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0143

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

(source)

DANN

Benign

0.47

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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