1-43966828-C-G

Variant names:

• chr1-43966828-C-G
• rs4660759
• NM_014652.4:c.2523+46C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4	c.2523+46C>G		intron_variant	Intron 17 of 19	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.1620+46C>G		intron_variant	Intron 16 of 18		XP_024306837.1
IPO13	XM_024451070.2	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	c.2523+46C>G		intron_variant	Intron 17 of 19	1	NM_014652.4	ENSP00000361418.3
IPO13	ENST00000372339.3	c.177+46C>G		intron_variant	Intron 2 of 4	2		ENSP00000361414.3

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95421 AN: 151880 Hom.: 33240 Cov.: 32

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

GnomAD2 exomes AF: 0.686 AC: 170950 AN: 249186 AF XY: 0.695

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 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.: 33 AF XY: 0.751 AC XY: 545428 AN XY: 725822

African (AFR) AF: 0.296 AC: 9898 AN: 33402

American (AMR) AF: 0.573 AC: 25523 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17912 AN: 26114

East Asian (EAS) AF: 0.572 AC: 22706 AN: 39676

South Asian (SAS) AF: 0.614 AC: 52962 AN: 86192

European-Finnish (FIN) AF: 0.790 AC: 42055 AN: 53260

Middle Eastern (MID) AF: 0.611 AC: 3521 AN: 5758

European-Non Finnish (NFE) AF: 0.795 AC: 881820 AN: 1109570

Other (OTH) AF: 0.716 AC: 43202 AN: 60318

GnomAD4 genome AF: 0.628 AC: 95456 AN: 151998 Hom.: 33247 Cov.: 32 AF XY: 0.626 AC XY: 46480 AN XY: 74308

African (AFR) AF: 0.318 AC: 13165 AN: 41434

American (AMR) AF: 0.623 AC: 9523 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2361 AN: 3466

East Asian (EAS) AF: 0.625 AC: 3216 AN: 5148

South Asian (SAS) AF: 0.604 AC: 2897 AN: 4798

European-Finnish (FIN) AF: 0.783 AC: 8287 AN: 10588

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53636 AN: 67966

Other (OTH) AF: 0.659 AC: 1391 AN: 2112

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
PhyloP100		-0.087
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4660759; hg19: chr1-44432500; COSMIC: COSV54837462; COSMIC: COSV54837462;