Variant rs12866550 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.-112-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 849,032 control chromosomes in the GnomAD database, including 3,128 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 0.049 ( 446 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2682 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

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:

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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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 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.-112-37C>T		intron_variant		ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2 linkuse as main transcript	c.-112-37C>T		intron_variant			NM_002271.6	ENSP00000499125	P1	O00410-1

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

7468

AN:

151970

Hom.:

444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0546

GnomAD3 exomes

AF:

0.0695

AC:

14721

AN:

211904

Hom.:

1170

AF XY:

0.0721

AC XY:

8304

AN XY:

115160

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0598

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.0412

Gnomad NFE exome

AF:

0.0411

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0611

AC:

42553

AN:

696944

Hom.:

2682

Cov.:

AF XY:

0.0643

AC XY:

24059

AN XY:

373906

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.0251

Gnomad4 ASJ exome

AF:

0.0604

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0434

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0650

GnomAD4 genome

AF:

0.0491

AC:

7470

AN:

152088

Hom.:

446

Cov.:

AF XY:

0.0522

AC XY:

3877

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.0330

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0418

Gnomad4 NFE

AF:

0.0388

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0428

Hom.:

Bravo

AF:

0.0475

Asia WGS

AF:

0.222

AC:

772

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.1

DANN

Benign

0.46

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