rs57918250

Positions:

• chr13-97969933-A-C
• chr13-97969933-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.-5+103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 817,148 control chromosomes in the GnomAD database, including 75,824 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 0.36 (11253 hom., cov: 32)
  • Exomes 𝑓: 0.43 (64571 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6	c.-5+103A>C		intron_variant		ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.-5+103A>C		intron_variant			NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54896 AN: 151766 Hom.: 11253 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.425 AC: 283022 AN: 665264 Hom.: 64571 Cov.: 9 AF XY: 0.426 AC XY: 148825 AN XY: 349294

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.361 AC: 54893 AN: 151884 Hom.: 11253 Cov.: 32 AF XY: 0.358 AC XY: 26606 AN XY: 74236

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.0223

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.337

Alfa AF: 0.307 Hom.: 902

Bravo AF: 0.341

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57918250; hg19: chr13-98622187;