rs12279202

Variant names:

• chr11-9410543-C-T
• rs12279202
• NM_006391.3:c.479+457C>T

Variant summary

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

The NM_006391.3(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 NM_006391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO7	NM_006391.3	MANE Select	c.479+457C>T		intron	N/A	NP_006382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO7	ENST00000379719.8	TSL:1 MANE Select	c.479+457C>T		intron	N/A	ENSP00000369042.3
	IPO7	ENST00000527431.1	TSL:4	c.293+457C>T		intron	N/A	ENSP00000435235.1
	IPO7	ENST00000528833.1	TSL:5	n.18+457C>T		intron	N/A

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

African (AFR) AF: 0.0128 AC: 530 AN: 41410

American (AMR) AF: 0.0351 AC: 536 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3472

East Asian (EAS) AF: 0.000776 AC: 4 AN: 5156

South Asian (SAS) AF: 0.0778 AC: 374 AN: 4808

European-Finnish (FIN) AF: 0.0534 AC: 562 AN: 10524

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4814 AN: 67938

Other (OTH) AF: 0.0421 AC: 89 AN: 2112

Alfa AF: 0.0612 Hom.: 101

Bravo AF: 0.0429

Asia WGS AF: 0.0230 AC: 81 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.63
PhyloP100		-0.023
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: rs12279202; hg19: chr11-9432090;