rs2289300

Variant names:

• chr12-30632251-T-A
• rs2289300
• NM_006390.4:c.2900-240A>T

Variant summary

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

The NM_006390.4(IPO8):​c.2900-240A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,920 control chromosomes in the GnomAD database, including 21,736 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 0.53 (21736 hom., cov: 31)
• Consequence: IPO8 NM_006390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 6 publications found

Genes affected

IPO8 (HGNC:9853): (importin 8) The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

IPO8 Gene-Disease associations (from GenCC):

• VISS syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO8	NM_006390.4	c.2900-240A>T		intron_variant	Intron 23 of 24	ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2285-240A>T		intron_variant	Intron 19 of 20		NP_001177924.1
IPO8	XM_017018691.3	c.2849-240A>T		intron_variant	Intron 23 of 24		XP_016874180.1
IPO8	XM_017018692.2	c.2714-240A>T		intron_variant	Intron 22 of 23		XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO8	ENST00000256079.9	c.2900-240A>T		intron_variant	Intron 23 of 24	1	NM_006390.4	ENSP00000256079.4
IPO8	ENST00000544829.5	c.2285-240A>T		intron_variant	Intron 19 of 20	2		ENSP00000444520.1
IPO8	ENST00000535598.1	c.371-240A>T		intron_variant	Intron 2 of 2	3		ENSP00000446232.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80428 AN: 151802 Hom.: 21719 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.530 AC: 80469 AN: 151920 Hom.: 21736 Cov.: 31 AF XY: 0.526 AC XY: 39073 AN XY: 74256

African (AFR) AF: 0.611 AC: 25308 AN: 41428

American (AMR) AF: 0.372 AC: 5683 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1925 AN: 3464

East Asian (EAS) AF: 0.443 AC: 2293 AN: 5172

South Asian (SAS) AF: 0.412 AC: 1981 AN: 4812

European-Finnish (FIN) AF: 0.591 AC: 6230 AN: 10542

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.523 AC: 35524 AN: 67930

Other (OTH) AF: 0.506 AC: 1066 AN: 2106

Alfa AF: 0.537 Hom.: 2745

Bravo AF: 0.513

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.78
PhyloP100		-0.0060
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: rs2289300; hg19: chr12-30785185;