1-43963008-G-C

Variant names:

• chr1-43963008-G-C
• rs1636879
• NM_014652.4:c.2345-1261G>C

Variant summary

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

The NM_014652.4(IPO13):​c.2345-1261G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,198 control chromosomes in the GnomAD database, including 1,709 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 0.14 (1709 hom., cov: 33)
• Consequence: IPO13 NM_014652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4	c.2345-1261G>C		intron_variant	Intron 14 of 19	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.1442-1261G>C		intron_variant	Intron 13 of 18		XP_024306837.1
IPO13	XM_024451070.2	c.1442-1261G>C		intron_variant	Intron 13 of 18		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.2345-1261G>C		intron_variant	Intron 14 of 19	1	NM_014652.4	ENSP00000361418.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21345 AN: 152080 Hom.: 1708 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.140 AC: 21363 AN: 152198 Hom.: 1709 Cov.: 33 AF XY: 0.142 AC XY: 10560 AN XY: 74422

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0950

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0439 Hom.: 46

Bravo AF: 0.150

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.74

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: rs1636879; hg19: chr1-44428680;