rs61970445

Variant names:

• chr13-98002421-G-A
• rs61970445
• NM_002271.6:c.1109-46G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002271.6(IPO5):​c.1109-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,589,462 control chromosomes in the GnomAD database, including 9,829 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 0.078 (638 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9191 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1109-46G>A		intron_variant	Intron 13 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.1109-46G>A		intron_variant	Intron 13 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11879 AN: 152156 Hom.: 636 Cov.: 33

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0813

GnomAD2 exomes AF: 0.0820 AC: 20027 AN: 244334 AF XY: 0.0823

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0853

GnomAD4 exome AF: 0.105 AC: 151431 AN: 1437188 Hom.: 9191 Cov.: 28 AF XY: 0.103 AC XY: 73645 AN XY: 715862

African (AFR) AF: 0.0147 AC: 481 AN: 32756

American (AMR) AF: 0.0464 AC: 1998 AN: 43016

Ashkenazi Jewish (ASJ) AF: 0.0587 AC: 1506 AN: 25640

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39592

South Asian (SAS) AF: 0.0298 AC: 2517 AN: 84428

European-Finnish (FIN) AF: 0.140 AC: 7480 AN: 53250

Middle Eastern (MID) AF: 0.0585 AC: 333 AN: 5694

European-Non Finnish (NFE) AF: 0.120 AC: 131643 AN: 1093292

Other (OTH) AF: 0.0919 AC: 5467 AN: 59520

GnomAD4 genome AF: 0.0780 AC: 11881 AN: 152274 Hom.: 638 Cov.: 33 AF XY: 0.0750 AC XY: 5581 AN XY: 74460

African (AFR) AF: 0.0191 AC: 792 AN: 41570

American (AMR) AF: 0.0568 AC: 868 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 215 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4828

European-Finnish (FIN) AF: 0.138 AC: 1466 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8166 AN: 68004

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

Alfa AF: 0.0701 Hom.: 151

Bravo AF: 0.0695

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.79
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs61970445; hg19: chr13-98654675;