rs633161

Variant names:

• chr13-98006104-G-A
• rs633161
• NM_002271.6:c.1498-26G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-98006104-G-A
• chr13-98006104-G-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.1498-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,467,068 control chromosomes in the GnomAD database, including 246,574 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 0.63 (31776 hom., cov: 31)
  • Exomes 𝑓: 0.57 (214798 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1498-26G>A		intron_variant	Intron 16 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.1498-26G>A		intron_variant	Intron 16 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95789 AN: 151862 Hom.: 31717 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.571

GnomAD2 exomes AF: 0.550 AC: 136375 AN: 247806 AF XY: 0.552

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.536

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.567 AC: 746228 AN: 1315088 Hom.: 214798 Cov.: 19 AF XY: 0.569 AC XY: 376423 AN XY: 662020

African (AFR) AF: 0.866 AC: 26166 AN: 30204

American (AMR) AF: 0.387 AC: 16927 AN: 43712

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 12884 AN: 25148

East Asian (EAS) AF: 0.545 AC: 21175 AN: 38878

South Asian (SAS) AF: 0.599 AC: 49393 AN: 82510

European-Finnish (FIN) AF: 0.534 AC: 28304 AN: 53034

Middle Eastern (MID) AF: 0.515 AC: 2821 AN: 5480

European-Non Finnish (NFE) AF: 0.568 AC: 556606 AN: 980762

Other (OTH) AF: 0.577 AC: 31952 AN: 55360

GnomAD4 genome AF: 0.631 AC: 95893 AN: 151980 Hom.: 31776 Cov.: 31 AF XY: 0.626 AC XY: 46490 AN XY: 74282

African (AFR) AF: 0.856 AC: 35511 AN: 41496

American (AMR) AF: 0.476 AC: 7270 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2886 AN: 5152

South Asian (SAS) AF: 0.602 AC: 2899 AN: 4818

European-Finnish (FIN) AF: 0.538 AC: 5678 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37999 AN: 67930

Other (OTH) AF: 0.571 AC: 1203 AN: 2106

Alfa AF: 0.582 Hom.: 19130

Bravo AF: 0.633

Asia WGS AF: 0.621 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		0.071
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs633161; hg19: chr13-98658358; COSMIC: COSV55155030;