rs12279202

Positions:

• chr11-9410543-C-T

Variant summary

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

The ENST00000379719.8(IPO7):​c.479+457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 151,880 control chromosomes in the GnomAD database, including 240 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 0.048 (240 hom., cov: 33)
• Consequence: IPO7 ENST00000379719.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

IPO7 (HGNC:9852): (importin 7) 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. Similar to importin-beta, this protein prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP, and also binds directly to nuclear pore complexes where it competes for binding sites with importin-beta and transportin. This protein has a Ran-dependent transport cycle and it can cross the nuclear envelope rapidly and in both directions. At least four importin beta-like transport receptors, namely importin beta itself, transportin, RanBP5 and RanBP7, directly bind and import ribosomal proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO7	NM_006391.3	c.479+457C>T		intron_variant		ENST00000379719.8	NP_006382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO7	ENST00000379719.8	c.479+457C>T		intron_variant		1	NM_006391.3	ENSP00000369042	P1
IPO7	ENST00000527431.1	c.293+457C>T		intron_variant		4		ENSP00000435235
IPO7	ENST00000528833.1	n.18+457C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7232 AN: 151762 Hom.: 240 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0476 AC: 7229 AN: 151880 Hom.: 240 Cov.: 33 AF XY: 0.0469 AC XY: 3483 AN XY: 74210

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0563 Hom.: 54

Bravo AF: 0.0429

Asia WGS AF: 0.0230 AC: 81 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.63

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: rs12279202; hg19: chr11-9432090;