NM_003400.4:c.302-2033C>T

Variant names:

• chr2-61504343-G-A
• rs6735330
• NM_003400.4:c.302-2033C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XPO1	NM_003400.4	c.302-2033C>T		intron_variant	Intron 4 of 24	ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.302-2033C>T		intron_variant	Intron 4 of 24	1	NM_003400.4	ENSP00000384863.2

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

African (AFR) AF: 0.288 AC: 11961 AN: 41480

American (AMR) AF: 0.111 AC: 1688 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3470

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5176

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4828

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9740 AN: 67996

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.147 Hom.: 7867

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
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6735330; hg19: chr2-61731478;