Variant 2-61492047-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003400.4(XPO1):c.1875T>G(p.Leu625=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,614,188 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

XPO1
NM_003400.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.75

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 2-61492047-A-C is Benign according to our data. Variant chr2-61492047-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 720238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.75 with no splicing effect.

BS2

High AC in GnomAd4 at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO1	NM_003400.4 linkuse as main transcript	c.1875T>G	p.Leu625=	synonymous_variant	16/25	ENST00000401558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO1	ENST00000401558.7 linkuse as main transcript	c.1875T>G	p.Leu625=	synonymous_variant	16/25	1	NM_003400.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000768

AC:

117

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000952

AC:

239

AN:

251158

Hom.:

AF XY:

0.00103

AC XY:

140

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00112

AC:

1639

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

846

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000881

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152374

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.000869

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.2

DANN

Benign

0.77

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over