Variant rs568379 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002271.6(IPO5):c.914-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,061,260 control chromosomes in the GnomAD database, including 3,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 697 hom., cov: 33)

Exomes 𝑓: 0.060 ( 3212 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

IPO5 (HGNC:6402): (importin 5) Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family. [provided by RefSeq, Jul 2008]

IPO5 links:

IPO5 (HGNC:):

IPO5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6 linkuse as main transcript	c.914-45A>C		intron_variant		ENST00000651721.2	NP_002262.4	O00410-1Q9BVS9B3KWG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2 linkuse as main transcript	c.914-45A>C		intron_variant			NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.0752

AC:

11437

AN:

152178

Hom.:

695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0394

Gnomad OTH

AF:

0.0689

GnomAD3 exomes

AF:

0.0774

AC:

16943

AN:

218828

Hom.:

1380

AF XY:

0.0789

AC XY:

9376

AN XY:

118838

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.0656

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.0409

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0666

GnomAD4 exome

AF:

0.0598

AC:

54317

AN:

908964

Hom.:

3212

Cov.:

AF XY:

0.0619

AC XY:

29190

AN XY:

471824

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0307

Gnomad4 ASJ exome

AF:

0.0645

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0429

Gnomad4 NFE exome

AF:

0.0404

Gnomad4 OTH exome

AF:

0.0730

GnomAD4 genome

AF:

0.0752

AC:

11454

AN:

152296

Hom.:

697

Cov.:

AF XY:

0.0772

AC XY:

5752

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.0734

Alfa

AF:

0.0371

Hom.:

Bravo

AF:

0.0776

Asia WGS

AF:

0.232

AC:

804

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

DANN

Benign

0.65

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over