NM_006391.3:c.479+253G>A

Variant names:

• chr11-9410339-G-A
• rs7480643
• NM_006391.3:c.479+253G>A

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+253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,930 control chromosomes in the GnomAD database, including 25,621 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 0.57 (25621 hom., cov: 32)
• Consequence: IPO7 NM_006391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 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+253G>A		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+253G>A		intron	N/A	ENSP00000369042.3
	IPO7	ENST00000970585.1		c.479+253G>A		intron	N/A	ENSP00000640644.1
	IPO7	ENST00000877280.1		c.479+253G>A		intron	N/A	ENSP00000547339.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86514 AN: 151810 Hom.: 25605 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.570 AC: 86578 AN: 151930 Hom.: 25621 Cov.: 32 AF XY: 0.563 AC XY: 41778 AN XY: 74234

African (AFR) AF: 0.471 AC: 19521 AN: 41432

American (AMR) AF: 0.588 AC: 8983 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5162

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4820

European-Finnish (FIN) AF: 0.587 AC: 6179 AN: 10518

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44112 AN: 67952

Other (OTH) AF: 0.567 AC: 1192 AN: 2102

Alfa AF: 0.629 Hom.: 39375

Bravo AF: 0.565

Asia WGS AF: 0.383 AC: 1332 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		-0.043
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7480643; hg19: chr11-9431886;