Variant 2-61484076-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003400.4(XPO1):c.2538G>A(p.Thr846=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,613,336 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 84 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 89 hom. )

Consequence

XPO1
NM_003400.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.583

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 2-61484076-C-T is Benign according to our data. Variant chr2-61484076-C-T is described in ClinVar as [Benign]. Clinvar id is 775172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.583 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO1	NM_003400.4 linkuse as main transcript	c.2538G>A	p.Thr846=	synonymous_variant	21/25	ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7 linkuse as main transcript	c.2538G>A	p.Thr846=	synonymous_variant	21/25	1	NM_003400.4	ENSP00000384863	P1
USP34-DT	ENST00000692738.1 linkuse as main transcript	n.719C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2855

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00552

AC:

1387

AN:

251072

Hom.:

AF XY:

0.00402

AC XY:

545

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.0697

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00212

AC:

3097

AN:

1461182

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1375

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.00513

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.0188

AC:

2861

AN:

152154

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1298

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0639

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00600

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.42

CADD

Benign

3.5

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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