Genetic Variant IPO13:c.2523+46C>G (chr1-43966828-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014652.4(IPO13):c.2523+46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,610,802 control chromosomes in the GnomAD database, including 455,344 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 ( 33247 hom., cov: 32)

Exomes 𝑓: 0.75 ( 422097 hom. )

Consequence

IPO13
NM_014652.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Variant links:

Genes affected

IPO13 (HGNC:16853): (importin 13) This gene encodes a member of the importin-beta family of nuclear transport proteins. The encoded protein mediates the import of specific cargo proteins from the cytoplasm to the nucleus and is dependent on the Ras-related nuclear protein-GTPase system. The encoded protein is also involved in nuclear export of the eukaryotic translation initiation factor 1A.[provided by RefSeq, Mar 2009]

IPO13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4 link	c.2523+46C>G	intron_variant	Intron 17 of 19	ENST00000372343.8	NP_055467.3	O94829
IPO13	XM_024451069.2 link	c.1620+46C>G	intron_variant	Intron 16 of 18		XP_024306837.1
IPO13	XM_024451070.2 link	c.1620+46C>G	intron_variant	Intron 16 of 18		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8 link	c.2523+46C>G		intron_variant	Intron 17 of 19	1	NM_014652.4	ENSP00000361418.3		O94829
IPO13	ENST00000372339.3 link	c.177+46C>G		intron_variant	Intron 2 of 4	2		ENSP00000361414.3		Q5T4X2

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95421

AN:

151880

Hom.:

33240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.783

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.789

Gnomad OTH

AF:

0.657

GnomAD3 exomes

AF:

0.686

AC:

170950

AN:

249186

Hom.:

60970

AF XY:

0.695

AC XY:

93714

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.683

Gnomad EAS exome

AF:

0.645

Gnomad SAS exome

AF:

0.606

Gnomad FIN exome

AF:

0.788

Gnomad NFE exome

AF:

0.785

Gnomad OTH exome

AF:

0.700

GnomAD4 exome

AF:

0.754

AC:

1099599

AN:

1458804

Hom.:

422097

Cov.:

AF XY:

0.751

AC XY:

545428

AN XY:

725822

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.572

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.790

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.716

GnomAD4 genome

AF:

0.628

AC:

95456

AN:

151998

Hom.:

33247

Cov.:

AF XY:

0.626

AC XY:

46480

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.783

Gnomad4 NFE

AF:

0.789

Gnomad4 OTH

AF:

0.659

Alfa

AF:

0.706

Hom.:

7353

Bravo

AF:

0.606

Asia WGS

AF:

0.607

AC:

2113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over