rs2301993

Positions:

• chr1-43960353-G-A
• chr1-43960353-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014652.4(IPO13):​c.2109+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,605,036 control chromosomes in the GnomAD database, including 452,490 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 0.62 (32994 hom., cov: 31)
  • Exomes 𝑓: 0.75 (419496 hom.)
• Consequence: IPO13 NM_014652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO13	NM_014652.4	c.2109+24G>A		intron_variant		ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.1206+24G>A		intron_variant			XP_024306837.1
IPO13	XM_024451070.2	c.1206+24G>A		intron_variant			XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.2109+24G>A		intron_variant		1	NM_014652.4	ENSP00000361418.3

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94857 AN: 151838 Hom.: 32995 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.683 AC: 171653 AN: 251172 Hom.: 61178 AF XY: 0.693 AC XY: 94076 AN XY: 135752

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.644

Gnomad SAS exome AF: 0.606

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.783

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.753 AC: 1093766 AN: 1453080 Hom.: 419496 Cov.: 29 AF XY: 0.750 AC XY: 542950 AN XY: 723484

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.794

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.624 AC: 94878 AN: 151956 Hom.: 32994 Cov.: 31 AF XY: 0.622 AC XY: 46190 AN XY: 74252

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.656

Alfa AF: 0.739 Hom.: 25698

Bravo AF: 0.602

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs2301993; hg19: chr1-44426025;