rs12866550

Variant names:

• chr13-97969686-C-T
• rs12866550
• NM_002271.6:c.-112-37C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002271.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	NM_002271.6	MANE Select	c.-112-37C>T		intron	N/A	NP_002262.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	ENST00000651721.2	MANE Select	c.-112-37C>T		intron	N/A	ENSP00000499125.1
	IPO5	ENST00000261574.10	TSL:1	c.-58-37C>T		intron	N/A	ENSP00000261574.5
	IPO5	ENST00000357602.7	TSL:5	c.-219-37C>T		intron	N/A	ENSP00000350219.3

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7468 AN: 151970 Hom.: 444 Cov.: 32

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

GnomAD2 exomes AF: 0.0695 AC: 14721 AN: 211904 AF XY: 0.0721

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 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.: 9 AF XY: 0.0643 AC XY: 24059 AN XY: 373906

African (AFR) AF: 0.0234 AC: 402 AN: 17152

American (AMR) AF: 0.0251 AC: 965 AN: 38496

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 1280 AN: 21176

East Asian (EAS) AF: 0.272 AC: 9226 AN: 33912

South Asian (SAS) AF: 0.136 AC: 8896 AN: 65240

European-Finnish (FIN) AF: 0.0434 AC: 2272 AN: 52376

Middle Eastern (MID) AF: 0.0586 AC: 254 AN: 4334

European-Non Finnish (NFE) AF: 0.0395 AC: 16969 AN: 429056

Other (OTH) AF: 0.0650 AC: 2289 AN: 35202

GnomAD4 genome AF: 0.0491 AC: 7470 AN: 152088 Hom.: 446 Cov.: 32 AF XY: 0.0522 AC XY: 3877 AN XY: 74320

African (AFR) AF: 0.0234 AC: 972 AN: 41456

American (AMR) AF: 0.0330 AC: 504 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1672 AN: 5166

South Asian (SAS) AF: 0.161 AC: 775 AN: 4824

European-Finnish (FIN) AF: 0.0418 AC: 442 AN: 10576

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2640 AN: 68012

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0424 Hom.: 30

Bravo AF: 0.0475

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-0.14
PromoterAI		-0.015	Neutral
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: rs12866550; hg19: chr13-98621940; COSMIC: COSV55152972; COSMIC: COSV55152972;