rs2906596

Positions:

• chr1-43961276-G-A
• chr1-43961276-G-C
• chr1-43961276-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.2344+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,603,624 control chromosomes in the GnomAD database, including 665,196 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 0.86 (56468 hom., cov: 32)
  • Exomes 𝑓: 0.91 (608728 hom.)
• Consequence: IPO13 NM_014652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO13	NM_014652.4	c.2344+14G>A		intron_variant		ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.1441+14G>A		intron_variant			XP_024306837.1
IPO13	XM_024451070.2	c.1441+14G>A		intron_variant			XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.2344+14G>A		intron_variant		1	NM_014652.4	ENSP00000361418	P1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130163 AN: 152048 Hom.: 56447 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.866

GnomAD3 exomes AF: 0.889 AC: 223284 AN: 251222 Hom.: 99706 AF XY: 0.895 AC XY: 121516 AN XY: 135796

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.848

Gnomad SAS exome AF: 0.899

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.893

GnomAD4 exome AF: 0.915 AC: 1327551 AN: 1451458 Hom.: 608728 Cov.: 32 AF XY: 0.915 AC XY: 661721 AN XY: 722874

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.850

Gnomad4 ASJ exome AF: 0.928

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.899

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.931

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.856 AC: 130239 AN: 152166 Hom.: 56468 Cov.: 32 AF XY: 0.855 AC XY: 63582 AN XY: 74404

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.867

Alfa AF: 0.893 Hom.: 12554

Bravo AF: 0.849

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2906596; hg19: chr1-44426948;