dbSNP rs56411106: IPO5:c.913+101G>A (chr13-97993326-G-A) – 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.913+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 952,710 control chromosomes in the GnomAD database, including 89,805 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 0.36 ( 11301 hom., cov: 33)

Exomes 𝑓: 0.42 ( 78504 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.219

Publications

1 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.913+101G>A		intron_variant	Intron 11 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.913+101G>A		intron_variant	Intron 11 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55019

AN:

151974

Hom.:

11298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.338

GnomAD4 exome

AF:

0.425

AC:

340054

AN:

800618

Hom.:

78504

AF XY:

0.425

AC XY:

175425

AN XY:

413062

show subpopulations

African (AFR)

AF:

0.192

AC:

3796

AN:

19742

American (AMR)

AF:

0.275

AC:

8310

AN:

30188

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

6679

AN:

17884

East Asian (EAS)

AF:

0.0149

AC:

528

AN:

35540

South Asian (SAS)

AF:

0.350

AC:

20721

AN:

59214

European-Finnish (FIN)

AF:

0.472

AC:

17410

AN:

36872

Middle Eastern (MID)

AF:

0.352

AC:

1512

AN:

4290

European-Non Finnish (NFE)

AF:

0.476

AC:

265794

AN:

558808

Other (OTH)

AF:

0.402

AC:

15304

AN:

38080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8733

17466

26198

34931

43664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5456

10912

16368

21824

27280

<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:

0.362

AC:

55023

AN:

152092

Hom.:

11301

Cov.:

AF XY:

0.358

AC XY:

26643

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.204

AC:

8465

AN:

41506

American (AMR)

AF:

0.323

AC:

4937

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1292

AN:

3472

East Asian (EAS)

AF:

0.0224

AC:

116

AN:

5178

South Asian (SAS)

AF:

0.333

AC:

1604

AN:

4820

European-Finnish (FIN)

AF:

0.479

AC:

5055

AN:

10558

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32334

AN:

67964

Other (OTH)

AF:

0.335

AC:

706

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1713

3425

5138

6850

8563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.439

Hom.:

3113

Bravo

AF:

0.342

Asia WGS

AF:

0.178

AC:

618

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

1.7

(source)

DANN

Benign

0.73

PhyloP100

-0.22

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