9-128515490-CTTATTTT-C

Position:

• chr9-128515490-CTTATTTT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001003722.2(GLE1):​c.322-35_322-29del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,162,682 control chromosomes in the GnomAD database, including 37,221 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6060 hom., cov: 21)
  • Exomes 𝑓: 0.24 (31161 hom.)
• Consequence: GLE1 NM_001003722.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.45

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 -16 ACMG points.

• BP6: Variant 9-128515490-CTTATTTT-C is Benign according to our data. Variant chr9-128515490-CTTATTTT-C is described in ClinVar as [Benign]. Clinvar id is 256859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLE1	NM_001003722.2	c.322-35_322-29del		intron_variant		ENST00000309971.9	NP_001003722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLE1	ENST00000309971.9	c.322-35_322-29del		intron_variant		1	NM_001003722.2	ENSP00000308622	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40783 AN: 151498 Hom.: 6049 Cov.: 21

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.283 AC: 59611 AN: 210280 Hom.: 8637 AF XY: 0.280 AC XY: 32073 AN XY: 114352

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.242 AC: 245122 AN: 1011064 Hom.: 31161 AF XY: 0.244 AC XY: 126919 AN XY: 520328

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.269 AC: 40826 AN: 151618 Hom.: 6060 Cov.: 21 AF XY: 0.274 AC XY: 20265 AN XY: 74070

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.252

Alfa AF: 0.223 Hom.: 754

Bravo AF: 0.279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372645952; hg19: chr9-131277769;