1-43953874-T-C

Variant names:

• chr1-43953874-T-C
• rs2486014
• NM_014652.4:c.822-2446T>C

Variant summary

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

The NM_014652.4(IPO13):​c.822-2446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 152,244 control chromosomes in the GnomAD database, including 881 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 0.096 (881 hom., cov: 32)
• Consequence: IPO13 NM_014652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4	c.822-2446T>C		intron_variant	Intron 2 of 19	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.-82-2446T>C		intron_variant	Intron 1 of 18		XP_024306837.1
IPO13	XM_024451070.2	c.-83+391T>C		intron_variant	Intron 1 of 18		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.822-2446T>C		intron_variant	Intron 2 of 19	1	NM_014652.4	ENSP00000361418.3
IPO13	ENST00000489773.5	n.184-2446T>C		intron_variant	Intron 2 of 4	3
IPO13	ENST00000492152.5	n.267+391T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14617 AN: 152126 Hom.: 880 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0961 AC: 14624 AN: 152244 Hom.: 881 Cov.: 32 AF XY: 0.0985 AC XY: 7334 AN XY: 74434

African (AFR) AF: 0.0458 AC: 1902 AN: 41556

American (AMR) AF: 0.166 AC: 2536 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3470

East Asian (EAS) AF: 0.0956 AC: 494 AN: 5170

South Asian (SAS) AF: 0.196 AC: 944 AN: 4826

European-Finnish (FIN) AF: 0.0713 AC: 757 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6876 AN: 68002

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0929 Hom.: 118

Bravo AF: 0.0985

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		-0.044
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: rs2486014; hg19: chr1-44419546;