rs568379

Variant names:

• chr13-97997486-A-C
• rs568379
• NM_002271.6:c.914-45A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-97997486-A-C
• chr13-97997486-A-G
• chr13-97997486-A-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.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
• 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=-0.82).
• 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 rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.914-45A>C		intron_variant	Intron 11 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.914-45A>C		intron_variant	Intron 11 of 28		NM_002271.6	ENSP00000499125.1

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

GnomAD2 exomes AF: 0.0774 AC: 16943 AN: 218828 AF XY: 0.0789

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 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

African (AFR) AF: 0.114 AC: 2518 AN: 22048

American (AMR) AF: 0.0307 AC: 1182 AN: 38462

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1383 AN: 21428

East Asian (EAS) AF: 0.281 AC: 9755 AN: 34732

South Asian (SAS) AF: 0.135 AC: 8390 AN: 62102

European-Finnish (FIN) AF: 0.0429 AC: 2170 AN: 50622

Middle Eastern (MID) AF: 0.0660 AC: 299 AN: 4532

European-Non Finnish (NFE) AF: 0.0404 AC: 25631 AN: 634110

Other (OTH) AF: 0.0730 AC: 2989 AN: 40928

GnomAD4 genome AF: 0.0752 AC: 11454 AN: 152296 Hom.: 697 Cov.: 33 AF XY: 0.0772 AC XY: 5752 AN XY: 74464

African (AFR) AF: 0.111 AC: 4611 AN: 41550

American (AMR) AF: 0.0459 AC: 701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1717 AN: 5190

South Asian (SAS) AF: 0.161 AC: 778 AN: 4830

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2682 AN: 68040

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0384 Hom.: 38

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
PhyloP100		1.4
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: rs568379; hg19: chr13-98649740;