rs61751231

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006390.4(IPO8):c.2636G>A(p.Arg879Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0114 in 1,613,952 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 4 hom., cov: 32)

Exomes 𝑓: 0.012 ( 125 hom. )

Consequence

IPO8
NM_006390.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.85

Publications

8 publications found

Variant links:

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]

IPO8 Gene-Disease associations (from GenCC):

VISS syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

IPO8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042545497).

BP6

Variant 12-30637041-C-T is Benign according to our data. Variant chr12-30637041-C-T is described in ClinVar as Benign. ClinVar VariationId is 1701194.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00759 (1156/152226) while in subpopulation NFE AF = 0.0126 (860/68020). AF 95% confidence interval is 0.0119. There are 4 homozygotes in GnomAd4. There are 524 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006390.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO8	NM_006390.4	MANE Select	c.2636G>A	p.Arg879Lys	missense	Exon 22 of 25	NP_006381.2
	IPO8	NM_001190995.2		c.2021G>A	p.Arg674Lys	missense	Exon 18 of 21	NP_001177924.1	O15397-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IPO8	ENST00000256079.9	TSL:1 MANE Select	c.2636G>A	p.Arg879Lys	missense	Exon 22 of 25	ENSP00000256079.4	O15397-1
IPO8	ENST00000910950.1		c.2732G>A	p.Arg911Lys	missense	Exon 23 of 26	ENSP00000581009.1
IPO8	ENST00000910953.1		c.2729G>A	p.Arg910Lys	missense	Exon 23 of 26	ENSP00000581012.1

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1155

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00831

AC:

2087

AN:

251102

AF XY:

0.00861

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00768

GnomAD4 exome

AF:

0.0118

AC:

17232

AN:

1461726

Hom.:

125

Cov.:

AF XY:

0.0117

AC XY:

8494

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

33480

American (AMR)

AF:

0.00465

AC:

208

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39686

South Asian (SAS)

AF:

0.00678

AC:

585

AN:

86256

European-Finnish (FIN)

AF:

0.00468

AC:

250

AN:

53410

Middle Eastern (MID)

AF:

0.00693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0140

AC:

15513

AN:

1111878

Other (OTH)

AF:

0.00886

AC:

535

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

833

1666

2498

3331

4164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00759

AC:

1156

AN:

152226

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

524

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00243

AC:

101

AN:

41526

American (AMR)

AF:

0.00530

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00540

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00368

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

860

AN:

68020

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0115

Hom.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00864

AC:

1049

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.12

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

3.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.67

REVEL

Benign

0.11

Sift

Benign

0.31

Sift4G

Benign

0.25

Polyphen

0.10

Vest4

0.22

MVP

0.42

MPC

0.27

ClinPred

0.019

GERP RS

3.2

PromoterAI

0.0048

Neutral

(source)

Varity_R

0.071

gMVP

0.33

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over