rs2301992

chr1-43961151-C-T

Variant summary

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

The NM_014652.4(IPO13):c.2248-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 1,611,952 control chromosomes in the GnomAD database, including 3,077 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 0.077 (684 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2393 hom.)
• Consequence: IPO13 NM_014652.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO13	NM_014652.4	c.2248-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000372343.8
IPO13	XM_024451069.2	c.1345-15C>T		splice_polypyrimidine_tract_variant, intron_variant
IPO13	XM_024451070.2	c.1345-15C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO13	ENST00000372343.8	c.2248-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014652.4	P1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11747 AN: 152062 Hom.: 684 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0690

GnomAD3 exomes AF: 0.0617 AC: 15510 AN: 251440 Hom.: 665 AF XY: 0.0606 AC XY: 8239 AN XY: 135898

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0667

Gnomad ASJ exome AF: 0.0231

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.0962

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0497 AC: 72534 AN: 1459772 Hom.: 2393 Cov.: 31 AF XY: 0.0504 AC XY: 36642 AN XY: 726360

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0646

Gnomad4 ASJ exome AF: 0.0240

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0928

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0412

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.0773 AC: 11759 AN: 152180 Hom.: 684 Cov.: 33 AF XY: 0.0773 AC XY: 5749 AN XY: 74394

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0669

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0474 Hom.: 236

Bravo AF: 0.0821

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	13
Dann	Benign	0.51

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: rs2301992; hg19: chr1-44426823; COSMIC: COSV64893086; COSMIC: COSV64893086;