NM_003400.4:c.888+9A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003400.4(XPO1):​c.888+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,577,470 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 15 hom. )

Consequence

XPO1
NM_003400.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.313
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 2-61496870-T-C is Benign according to our data. Variant chr2-61496870-T-C is described in ClinVar as [Benign]. Clinvar id is 775721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00767 (1168/152366) while in subpopulation AFR AF= 0.0269 (1118/41586). AF 95% confidence interval is 0.0256. There are 20 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1168 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XPO1NM_003400.4 linkc.888+9A>G intron_variant Intron 10 of 24 ENST00000401558.7 NP_003391.1 O14980B3KWD0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XPO1ENST00000401558.7 linkc.888+9A>G intron_variant Intron 10 of 24 1 NM_003400.4 ENSP00000384863.2 O14980

Frequencies

GnomAD3 genomes
AF:
0.00767
AC:
1168
AN:
152248
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0270
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00193
AC:
424
AN:
219172
Hom.:
3
AF XY:
0.00132
AC XY:
157
AN XY:
119086
show subpopulations
Gnomad AFR exome
AF:
0.0261
Gnomad AMR exome
AF:
0.000922
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000386
Gnomad OTH exome
AF:
0.000757
GnomAD4 exome
AF:
0.000735
AC:
1048
AN:
1425104
Hom.:
15
Cov.:
30
AF XY:
0.000602
AC XY:
426
AN XY:
707730
show subpopulations
Gnomad4 AFR exome
AF:
0.0286
Gnomad4 AMR exome
AF:
0.00108
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000503
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.00136
GnomAD4 genome
AF:
0.00767
AC:
1168
AN:
152366
Hom.:
20
Cov.:
32
AF XY:
0.00742
AC XY:
553
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.0269
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00336
Hom.:
3
Bravo
AF:
0.00855
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.3
DANN
Benign
0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140857799; hg19: chr2-61724005; API