Genetic Variant IPO5:c.2325+81T>C (chr13-98014295-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002271.6(IPO5):c.2325+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,038,698 control chromosomes in the GnomAD database, including 144,321 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 0.55 ( 24386 hom., cov: 31)

Exomes 𝑓: 0.51 ( 119935 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

2 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.2325+81T>C		intron_variant	Intron 22 of 28	ENST00000651721.2	NP_002262.4	O00410-1Q9BVS9B3KWG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2 link	c.2325+81T>C		intron_variant	Intron 22 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84192

AN:

151822

Hom.:

24352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.511

AC:

453273

AN:

886758

Hom.:

119935

AF XY:

0.511

AC XY:

230728

AN XY:

451402

show subpopulations

African (AFR)

AF:

0.748

AC:

14905

AN:

19934

American (AMR)

AF:

0.363

AC:

9207

AN:

25398

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

8692

AN:

17406

East Asian (EAS)

AF:

0.318

AC:

10736

AN:

33800

South Asian (SAS)

AF:

0.500

AC:

28174

AN:

56328

European-Finnish (FIN)

AF:

0.491

AC:

20465

AN:

41674

Middle Eastern (MID)

AF:

0.463

AC:

1938

AN:

4182

European-Non Finnish (NFE)

AF:

0.523

AC:

338719

AN:

647918

Other (OTH)

AF:

0.509

AC:

20437

AN:

40118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

10103

20205

30308

40410

50513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8056

16112

24168

32224

40280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.555

AC:

84271

AN:

151940

Hom.:

24386

Cov.:

AF XY:

0.549

AC XY:

40766

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.735

AC:

30465

AN:

41436

American (AMR)

AF:

0.433

AC:

6614

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1702

AN:

3464

East Asian (EAS)

AF:

0.293

AC:

1512

AN:

5164

South Asian (SAS)

AF:

0.472

AC:

2275

AN:

4818

European-Finnish (FIN)

AF:

0.499

AC:

5261

AN:

10540

Middle Eastern (MID)

AF:

0.448

AC:

130

AN:

290

European-Non Finnish (NFE)

AF:

0.513

AC:

34854

AN:

67944

Other (OTH)

AF:

0.504

AC:

1065

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1824

3647

5471

7294

9118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.383

Hom.:

951

Bravo

AF:

0.553

Asia WGS

AF:

0.417

AC:

1452

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.49

(source)

DANN

Benign

0.47

PhyloP100

-0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over