rs2585897

Variant names:

• chr13-20824840-G-A
• rs2585897
• NM_022459.5:c.840+2227C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

LOC124903129 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022459.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO4	NM_022459.5	MANE Select	c.840+2227C>T		intron	N/A	NP_071904.4
	XPO4	NM_001372061.1		c.840+2227C>T		intron	N/A	NP_001358990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO4	ENST00000255305.11	TSL:1 MANE Select	c.840+2227C>T		intron	N/A	ENSP00000255305.6	Q9C0E2
	XPO4	ENST00000909777.1		c.840+2227C>T		intron	N/A	ENSP00000579836.1
	XPO4	ENST00000953408.1		c.840+2227C>T		intron	N/A	ENSP00000623467.1

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

African (AFR) AF: 0.179 AC: 7412 AN: 41492

American (AMR) AF: 0.399 AC: 6091 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4142 AN: 5178

South Asian (SAS) AF: 0.454 AC: 2191 AN: 4824

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11735 AN: 67962

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.201 Hom.: 11812

Bravo AF: 0.240

Asia WGS AF: 0.590 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		0.39
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: rs2585897; hg19: chr13-21398979; COSMIC: COSV55005627;