12-30647419-T-C

Position:

• chr12-30647419-T-C

Variant summary

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

The NM_006390.4(IPO8):​c.2268+1718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,462 control chromosomes in the GnomAD database, including 24,545 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 0.56 (24545 hom., cov: 28)
• Consequence: IPO8 NM_006390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.66

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO8	NM_006390.4	c.2268+1718A>G		intron_variant		ENST00000256079.9
IPO8	NM_001190995.2	c.1653+1718A>G		intron_variant
IPO8	XM_017018691.3	c.2217+1718A>G		intron_variant
IPO8	XM_017018692.2	c.2082+1718A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO8	ENST00000256079.9	c.2268+1718A>G		intron_variant		1	NM_006390.4	P1
IPO8	ENST00000544829.5	c.1653+1718A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84547 AN: 151344 Hom.: 24524 Cov.: 28

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.559 AC: 84596 AN: 151462 Hom.: 24545 Cov.: 28 AF XY: 0.554 AC XY: 40981 AN XY: 73960

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.531

Alfa AF: 0.521 Hom.: 9321

Bravo AF: 0.547

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.29

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: rs3910564; hg19: chr12-30800353;