rs2585897

Positions:

• chr13-20824840-G-A
• chr13-20824840-G-C
• chr13-20824840-G-T

Variant summary

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

The NM_022459.5(XPO4):​c.840+2227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,090 control chromosomes in the GnomAD database, including 5,771 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 0.23 (5771 hom., cov: 32)
• Consequence: XPO4 NM_022459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392

Genes affected

XPO4 (HGNC:17796): (exportin 4) XPO4 belongs to a large family of karyopherins (see MIM 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments (Lipowsky et al., 2000 [PubMed 10944119]).[supplied by OMIM, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO4	NM_022459.5	c.840+2227C>T		intron_variant		ENST00000255305.11	NP_071904.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO4	ENST00000255305.11	c.840+2227C>T		intron_variant		1	NM_022459.5	ENSP00000255305.6

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35311 AN: 151972 Hom.: 5748 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.232 AC: 35356 AN: 152090 Hom.: 5771 Cov.: 32 AF XY: 0.247 AC XY: 18366 AN XY: 74354

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.208

Alfa AF: 0.200 Hom.: 9044

Bravo AF: 0.240

Asia WGS AF: 0.590 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.84

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: rs2585897; hg19: chr13-21398979; COSMIC: COSV55005627;