Genetic Variant NM_006391.3:c.479+457C>T (chr11-9410543-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Publications

15 publications found

Variant links:

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]

IPO7 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO7	NM_006391.3 link	c.479+457C>T		intron_variant	Intron 4 of 24	ENST00000379719.8	NP_006382.1	O95373B3KNG9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IPO7	ENST00000379719.8 link	c.479+457C>T	intron_variant	Intron 4 of 24	1	NM_006391.3	ENSP00000369042.3	O95373
IPO7	ENST00000527431.1 link	c.293+457C>T	intron_variant	Intron 3 of 3	4		ENSP00000435235.1	E9PLB2
IPO7	ENST00000528833.1 link	n.18+457C>T	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7232

AN:

151762

Hom.:

240

Cov.:

show subpopulations

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.:

AF XY:

0.0469

AC XY:

3483

AN XY:

74210

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0709

AC:

4814

AN:

67938

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

353

706

1060

1413

1766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0612

Hom.:

101

Bravo

AF:

0.0429

Asia WGS

AF:

0.0230

AC:

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

(source)

DANN

Benign

0.63

PhyloP100

-0.023

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over