rs1992765

Positions:

• chr2-61524198-A-G

Variant summary

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

The NM_003400.4(XPO1):​c.229-1515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,992 control chromosomes in the GnomAD database, including 28,845 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 0.62 (28845 hom., cov: 32)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO1	NM_003400.4	c.229-1515T>C		intron_variant		ENST00000401558.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO1	ENST00000401558.7	c.229-1515T>C		intron_variant		1	NM_003400.4	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93411 AN: 151874 Hom.: 28819 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.615 AC: 93492 AN: 151992 Hom.: 28845 Cov.: 32 AF XY: 0.615 AC XY: 45718 AN XY: 74284

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.636

Alfa AF: 0.606 Hom.: 4106

Bravo AF: 0.615

Asia WGS AF: 0.623 AC: 2162 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.71

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: rs1992765; hg19: chr2-61751333;