rs2585901

Variant names:

• chr13-20846132-G-A
• rs2585901
• NM_022459.5:c.457-2246C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-20846132-G-A
• chr13-20846132-G-C

Variant summary

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

The NM_022459.5(XPO4):​c.457-2246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,030 control chromosomes in the GnomAD database, including 8,370 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 0.30 (8370 hom., cov: 32)
• Consequence: XPO4 NM_022459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO4	NM_022459.5	c.457-2246C>T		intron_variant	Intron 4 of 22	ENST00000255305.11	NP_071904.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO4	ENST00000255305.11	c.457-2246C>T		intron_variant	Intron 4 of 22	1	NM_022459.5	ENSP00000255305.6

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44880 AN: 151912 Hom.: 8348 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.296 AC: 44945 AN: 152030 Hom.: 8370 Cov.: 32 AF XY: 0.308 AC XY: 22898 AN XY: 74326

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.263

Alfa AF: 0.253 Hom.: 722

Bravo AF: 0.311

Asia WGS AF: 0.610 AC: 2117 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	0.51
DANN	Benign	0.40

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: rs2585901; hg19: chr13-21420271;