Genetic Variant XPO1:c.*292G>A (chr2-61478528-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_003400.4(XPO1):c.*292G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 332,782 control chromosomes in the GnomAD database, including 3,414 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 0.11 ( 1294 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2120 hom. )

Consequence

XPO1
NM_003400.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

17 publications found

Variant links:

Genes affected

XPO1 (HGNC:12825): (exportin 1) This cell-cycle-regulated gene encodes a protein that mediates leucine-rich nuclear export signal (NES)-dependent protein transport. The protein specifically inhibits the nuclear export of Rev and U snRNAs. It is involved in the control of several cellular processes by controlling the localization of cyclin B, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1. [provided by RefSeq, Jan 2015]

XPO1 links:

USP34-DT (HGNC:55262): (USP34 divergent transcript)

USP34-DT 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=-0.7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO1	NM_003400.4 link	c.*292G>A		3_prime_UTR_variant	Exon 25 of 25	ENST00000401558.7	NP_003391.1	O14980B3KWD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7 link	c.*292G>A		3_prime_UTR_variant	Exon 25 of 25	1	NM_003400.4	ENSP00000384863.2		O14980

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16888

AN:

151930

Hom.:

1298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.0878

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.134

AC:

24305

AN:

180734

Hom.:

2120

Cov.:

AF XY:

0.137

AC XY:

12407

AN XY:

90424

show subpopulations

African (AFR)

AF:

0.0326

AC:

194

AN:

5958

American (AMR)

AF:

0.171

AC:

993

AN:

5822

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

1314

AN:

7398

East Asian (EAS)

AF:

0.297

AC:

4680

AN:

15750

South Asian (SAS)

AF:

0.274

AC:

1976

AN:

7220

European-Finnish (FIN)

AF:

0.0838

AC:

728

AN:

8690

Middle Eastern (MID)

AF:

0.124

AC:

110

AN:

884

European-Non Finnish (NFE)

AF:

0.109

AC:

12714

AN:

116536

Other (OTH)

AF:

0.128

AC:

1596

AN:

12476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1088

2176

3265

4353

5441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.111

AC:

16872

AN:

152048

Hom.:

1294

Cov.:

AF XY:

0.117

AC XY:

8669

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0347

AC:

1439

AN:

41490

American (AMR)

AF:

0.160

AC:

2443

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

616

AN:

3468

East Asian (EAS)

AF:

0.285

AC:

1474

AN:

5166

South Asian (SAS)

AF:

0.321

AC:

1548

AN:

4820

European-Finnish (FIN)

AF:

0.0878

AC:

927

AN:

10558

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7937

AN:

67980

Other (OTH)

AF:

0.124

AC:

261

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

747

1495

2242

2990

3737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.125

Hom.:

782

Bravo

AF:

0.112

Asia WGS

AF:

0.288

AC:

1002

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.36

(source)

DANN

Benign

0.57

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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