rs2240447

Variant names:

• chr1-43949743-C-T
• rs2240447
• NM_014652.4:c.411C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014652.4(IPO13):​c.411C>T​(p.Asp137Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,613,968 control chromosomes in the GnomAD database, including 453,584 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 0.59 (31800 hom., cov: 34)
  • Exomes 𝑓: 0.75 (421784 hom.)
• Consequence: IPO13 NM_014652.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 28 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.631 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4	c.411C>T	p.Asp137Asp	synonymous_variant	Exon 2 of 20	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.-83+2059C>T		intron_variant	Intron 1 of 18		XP_024306837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.411C>T	p.Asp137Asp	synonymous_variant	Exon 2 of 20	1	NM_014652.4	ENSP00000361418.3
IPO13	ENST00000489773.5	n.116-343C>T		intron_variant	Intron 1 of 4	3
IPO13	ENST00000489061.1	n.*198C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90040 AN: 152092 Hom.: 31799 Cov.: 34

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.677 AC: 170082 AN: 251152 AF XY: 0.689

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.683

Gnomad EAS exome AF: 0.644

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.750 AC: 1096966 AN: 1461760 Hom.: 421784 Cov.: 63 AF XY: 0.749 AC XY: 544625 AN XY: 727188

African (AFR) AF: 0.165 AC: 5519 AN: 33478

American (AMR) AF: 0.565 AC: 25277 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17920 AN: 26132

East Asian (EAS) AF: 0.572 AC: 22709 AN: 39698

South Asian (SAS) AF: 0.623 AC: 53727 AN: 86252

European-Finnish (FIN) AF: 0.789 AC: 42153 AN: 53398

Middle Eastern (MID) AF: 0.606 AC: 3497 AN: 5768

European-Non Finnish (NFE) AF: 0.794 AC: 883415 AN: 1111936

Other (OTH) AF: 0.708 AC: 42749 AN: 60394

GnomAD4 genome AF: 0.592 AC: 90055 AN: 152208 Hom.: 31800 Cov.: 34 AF XY: 0.591 AC XY: 43953 AN XY: 74412

African (AFR) AF: 0.191 AC: 7932 AN: 41536

American (AMR) AF: 0.610 AC: 9332 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3236 AN: 5164

South Asian (SAS) AF: 0.610 AC: 2943 AN: 4824

European-Finnish (FIN) AF: 0.783 AC: 8301 AN: 10596

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53630 AN: 68004

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.706 Hom.: 31170

Bravo AF: 0.564

Asia WGS AF: 0.600 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.29
DANN	Benign	0.81
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240447; hg19: chr1-44415415; COSMIC: COSV64894612; COSMIC: COSV64894612;