12-30632825-G-A

Variant names:

• chr12-30632825-G-A
• rs33270
• NM_006390.4:c.2900-814C>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.2900-814C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,254 control chromosomes in the GnomAD database, including 63,816 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 0.91 (63816 hom., cov: 32)
• Consequence: IPO8 NM_006390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO8	NM_006390.4	c.2900-814C>T		intron_variant	Intron 23 of 24	ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2285-814C>T		intron_variant	Intron 19 of 20		NP_001177924.1
IPO8	XM_017018691.3	c.2849-814C>T		intron_variant	Intron 23 of 24		XP_016874180.1
IPO8	XM_017018692.2	c.2714-814C>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.2900-814C>T		intron_variant	Intron 23 of 24	1	NM_006390.4	ENSP00000256079.4
IPO8	ENST00000544829.5	c.2285-814C>T		intron_variant	Intron 19 of 20	2		ENSP00000444520.1
IPO8	ENST00000535598.1	c.371-814C>T		intron_variant	Intron 2 of 2	3		ENSP00000446232.1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139059 AN: 152136 Hom.: 63749 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.914 AC: 139187 AN: 152254 Hom.: 63816 Cov.: 32 AF XY: 0.917 AC XY: 68251 AN XY: 74438

African (AFR) AF: 0.978 AC: 40658 AN: 41558

American (AMR) AF: 0.928 AC: 14202 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3185 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5184

South Asian (SAS) AF: 0.975 AC: 4705 AN: 4824

European-Finnish (FIN) AF: 0.872 AC: 9240 AN: 10596

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58979 AN: 68008

Other (OTH) AF: 0.907 AC: 1914 AN: 2110

Alfa AF: 0.903 Hom.: 49480

Bravo AF: 0.919

Asia WGS AF: 0.984 AC: 3420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.8
DANN	Benign	0.71
PhyloP100		-0.063
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: rs33270; hg19: chr12-30785759;