rs568379

Positions:

• chr13-97997486-A-C
• chr13-97997486-A-G
• chr13-97997486-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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]

ACMG classification

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	UniProt
IPO5	NM_002271.6	c.914-45A>C		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.914-45A>C		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11437 AN: 152178 Hom.: 695 Cov.: 33

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

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.: 12 AF XY: 0.0619 AC XY: 29190 AN XY: 471824

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.: 33 AF XY: 0.0772 AC XY: 5752 AN XY: 74464

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.: 34

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

Other links and lift over

dbSNP: rs568379; hg19: chr13-98649740;