Genetic Variant NM_015024.5:c.696C>T (chr8-21976454-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_015024.5(XPO7):c.696C>T(p.Ile232Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,512 control chromosomes in the GnomAD database, including 135,034 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 ( 10189 hom., cov: 32)

Exomes 𝑓: 0.41 ( 124845 hom. )

Consequence

XPO7
NM_015024.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.206

Publications

23 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=0.206 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO7	NM_015024.5 link	c.696C>T	p.Ile232Ile	synonymous_variant	Exon 7 of 28	ENST00000252512.14	NP_055839.3	Q9UIA9
XPO7	NM_001100161.2 link	c.723C>T	p.Ile241Ile	synonymous_variant	Exon 7 of 28		NP_001093631.1
XPO7	NM_001362802.2 link	c.630C>T	p.Ile210Ile	synonymous_variant	Exon 6 of 27		NP_001349731.1
XPO7	NR_156173.2 link	n.805C>T		non_coding_transcript_exon_variant	Exon 7 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XPO7	ENST00000252512.14 link	c.696C>T	p.Ile232Ile	synonymous_variant	Exon 7 of 28	1	NM_015024.5	ENSP00000252512.9	Q9UIA9
XPO7	ENST00000518017.1 link	n.891C>T		non_coding_transcript_exon_variant	Exon 7 of 7	1
XPO7	ENST00000433566.8 link	c.699C>T	p.Ile233Ile	synonymous_variant	Exon 7 of 28	5		ENSP00000410249.3	E7ESC6

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54005

AN:

151854

Hom.:

10188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.352

AC:

87746

AN:

249124

AF XY:

0.354

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.405

AC:

592505

AN:

1461540

Hom.:

124845

Cov.:

AF XY:

0.400

AC XY:

290760

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.263

AC:

8790

AN:

33472

American (AMR)

AF:

0.189

AC:

8473

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

10087

AN:

26132

East Asian (EAS)

AF:

0.355

AC:

14097

AN:

39694

South Asian (SAS)

AF:

0.194

AC:

16759

AN:

86246

European-Finnish (FIN)

AF:

0.447

AC:

23864

AN:

53392

Middle Eastern (MID)

AF:

0.329

AC:

1897

AN:

5766

European-Non Finnish (NFE)

AF:

0.436

AC:

484674

AN:

1111754

Other (OTH)

AF:

0.395

AC:

23864

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19227

38453

57680

76906

96133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14518

29036

43554

58072

72590

<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:

0.355

AC:

54024

AN:

151972

Hom.:

10189

Cov.:

AF XY:

0.351

AC XY:

26091

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.261

AC:

10818

AN:

41450

American (AMR)

AF:

0.257

AC:

3924

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1364

AN:

3468

East Asian (EAS)

AF:

0.404

AC:

2084

AN:

5162

South Asian (SAS)

AF:

0.189

AC:

909

AN:

4820

European-Finnish (FIN)

AF:

0.458

AC:

4828

AN:

10534

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28791

AN:

67942

Other (OTH)

AF:

0.368

AC:

777

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1751

3501

5252

7002

8753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.393

Hom.:

37346

Bravo

AF:

0.341

Asia WGS

AF:

0.328

AC:

1141

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

8.1

(source)

DANN

Benign

0.68

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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