Genetic Variant XPO7:c.259+75C>T (chr8-21969651-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_015024.5(XPO7):c.259+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,323,732 control chromosomes in the GnomAD database, including 111,543 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 0.36 ( 10581 hom., cov: 32)

Exomes 𝑓: 0.41 ( 100962 hom. )

Consequence

XPO7
NM_015024.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

8 publications found

Variant links:

Genes affected

XPO7 (HGNC:14108): (exportin 7) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-16 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

XPO7 Gene-Disease associations (from GenCC):

prostate cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

XPO7 links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
XPO7	NM_015024.5 link	c.259+75C>T	intron_variant	Intron 3 of 27	ENST00000252512.14	NP_055839.3	Q9UIA9
XPO7	NM_001100161.2 link	c.259+75C>T	intron_variant	Intron 3 of 27		NP_001093631.1
XPO7	NM_001362802.2 link	c.259+75C>T	intron_variant	Intron 3 of 26		NP_001349731.1
XPO7	NR_156173.2 link	n.368+75C>T	intron_variant	Intron 3 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14 link	c.259+75C>T		intron_variant	Intron 3 of 27	1	NM_015024.5	ENSP00000252512.9		Q9UIA9

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55402

AN:

151838

Hom.:

10578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.369

GnomAD4 exome

AF:

0.407

AC:

477072

AN:

1171776

Hom.:

100962

Cov.:

AF XY:

0.401

AC XY:

236051

AN XY:

588682

show subpopulations

African (AFR)

AF:

0.294

AC:

7988

AN:

27192

American (AMR)

AF:

0.201

AC:

6989

AN:

34758

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

8983

AN:

23014

East Asian (EAS)

AF:

0.351

AC:

12573

AN:

35796

South Asian (SAS)

AF:

0.196

AC:

14317

AN:

73090

European-Finnish (FIN)

AF:

0.448

AC:

20921

AN:

46692

Middle Eastern (MID)

AF:

0.333

AC:

1726

AN:

5190

European-Non Finnish (NFE)

AF:

0.438

AC:

383391

AN:

875348

Other (OTH)

AF:

0.398

AC:

20184

AN:

50696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13179

26357

39536

52714

65893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10718

21436

32154

42872

53590

<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:

0.365

AC:

55427

AN:

151956

Hom.:

10581

Cov.:

AF XY:

0.360

AC XY:

26760

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.291

AC:

12049

AN:

41410

American (AMR)

AF:

0.259

AC:

3955

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1370

AN:

3466

East Asian (EAS)

AF:

0.404

AC:

2088

AN:

5168

South Asian (SAS)

AF:

0.188

AC:

904

AN:

4814

European-Finnish (FIN)

AF:

0.459

AC:

4841

AN:

10558

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28900

AN:

67960

Other (OTH)

AF:

0.372

AC:

786

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.381

Hom.:

2327

Bravo

AF:

0.351

Asia WGS

AF:

0.331

AC:

1154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

(source)

DANN

Benign

0.56

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over