rs6735330

Positions:

• chr2-61504343-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003400.4(XPO1):​c.302-2033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,112 control chromosomes in the GnomAD database, including 2,734 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 0.17 (2734 hom., cov: 33)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO1	NM_003400.4	c.302-2033C>T		intron_variant		ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.302-2033C>T		intron_variant		1	NM_003400.4	ENSP00000384863	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25903 AN: 151994 Hom.: 2728 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25935 AN: 152112 Hom.: 2734 Cov.: 33 AF XY: 0.167 AC XY: 12381 AN XY: 74360

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.159

Alfa AF: 0.141 Hom.: 3390

Bravo AF: 0.176

Asia WGS AF: 0.0530 AC: 186 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.19

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

Other links and lift over

dbSNP: rs6735330; hg19: chr2-61731478;