chr2-61508311-C-T

Variant names:

• chr2-61508311-C-T
• rs766448
• NM_003400.4:c.302-6001G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003400.4(XPO1):​c.302-6001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,012 control chromosomes in the GnomAD database, including 13,542 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 0.40 (13542 hom., cov: 33)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO1	NM_003400.4	c.302-6001G>A		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.302-6001G>A		intron_variant	Intron 4 of 24	1	NM_003400.4	ENSP00000384863.2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61395 AN: 151894 Hom.: 13537 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.404 AC: 61423 AN: 152012 Hom.: 13542 Cov.: 33 AF XY: 0.411 AC XY: 30520 AN XY: 74290

African (AFR) AF: 0.224 AC: 9296 AN: 41458

American (AMR) AF: 0.449 AC: 6851 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3241 AN: 5176

South Asian (SAS) AF: 0.550 AC: 2655 AN: 4826

European-Finnish (FIN) AF: 0.468 AC: 4939 AN: 10544

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30831 AN: 67962

Other (OTH) AF: 0.446 AC: 941 AN: 2108

Alfa AF: 0.414 Hom.: 2264

Bravo AF: 0.394

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		0.26
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: rs766448; hg19: chr2-61735446;