12-30632251-T-A

Position:

• chr12-30632251-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IPO8	NM_006390.4	c.2900-240A>T		intron_variant		ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2285-240A>T		intron_variant			NP_001177924.1
IPO8	XM_017018691.3	c.2849-240A>T		intron_variant			XP_016874180.1
IPO8	XM_017018692.2	c.2714-240A>T		intron_variant			XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO8	ENST00000256079.9	c.2900-240A>T		intron_variant		1	NM_006390.4	ENSP00000256079	P1
IPO8	ENST00000535598.1	c.373-240A>T		intron_variant		3		ENSP00000446232
IPO8	ENST00000544829.5	c.2285-240A>T		intron_variant		2		ENSP00000444520

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

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.506

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

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: rs2289300; hg19: chr12-30785185;