rs2306641

Variant names:

• chr8-21976454-C-T
• rs2306641
• NM_015024.5:c.696C>T
• XPO7 p.Ile232Ile

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015024.5(XPO7):​c.696C>T​(p.Ile232Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,512 control chromosomes in the GnomAD database, including 135,034 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 0.36 (10189 hom., cov: 32)
  • Exomes 𝑓: 0.41 (124845 hom.)
• Consequence: XPO7 NM_015024.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 23 publications found

Genes affected

XPO7 (HGNC:14108): (exportin 7) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-16 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

XPO7 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.206 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015024.5. 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
	XPO7	NM_015024.5	MANE Select	c.696C>T	p.Ile232Ile	synonymous	Exon 7 of 28	NP_055839.3
	XPO7	NM_001100161.2		c.723C>T	p.Ile241Ile	synonymous	Exon 7 of 28	NP_001093631.1
	XPO7	NM_001362802.2		c.630C>T	p.Ile210Ile	synonymous	Exon 6 of 27	NP_001349731.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	ENST00000252512.14	TSL:1 MANE Select	c.696C>T	p.Ile232Ile	synonymous	Exon 7 of 28	ENSP00000252512.9	Q9UIA9
	XPO7	ENST00000518017.1	TSL:1	n.891C>T		non_coding_transcript_exon	Exon 7 of 7
	XPO7	ENST00000433566.8	TSL:5	c.699C>T	p.Ile233Ile	synonymous	Exon 7 of 28	ENSP00000410249.3	E7ESC6

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54005 AN: 151854 Hom.: 10188 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.352 AC: 87746 AN: 249124 AF XY: 0.354

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.405 AC: 592505 AN: 1461540 Hom.: 124845 Cov.: 47 AF XY: 0.400 AC XY: 290760 AN XY: 727060

African (AFR) AF: 0.263 AC: 8790 AN: 33472

American (AMR) AF: 0.189 AC: 8473 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 10087 AN: 26132

East Asian (EAS) AF: 0.355 AC: 14097 AN: 39694

South Asian (SAS) AF: 0.194 AC: 16759 AN: 86246

European-Finnish (FIN) AF: 0.447 AC: 23864 AN: 53392

Middle Eastern (MID) AF: 0.329 AC: 1897 AN: 5766

European-Non Finnish (NFE) AF: 0.436 AC: 484674 AN: 1111754

Other (OTH) AF: 0.395 AC: 23864 AN: 60368

GnomAD4 genome AF: 0.355 AC: 54024 AN: 151972 Hom.: 10189 Cov.: 32 AF XY: 0.351 AC XY: 26091 AN XY: 74274

African (AFR) AF: 0.261 AC: 10818 AN: 41450

American (AMR) AF: 0.257 AC: 3924 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2084 AN: 5162

South Asian (SAS) AF: 0.189 AC: 909 AN: 4820

European-Finnish (FIN) AF: 0.458 AC: 4828 AN: 10534

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28791 AN: 67942

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.393 Hom.: 37346

Bravo AF: 0.341

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.1
DANN	Benign	0.68
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2306641;

hg19: chr8-21833965;

COSMIC: COSV53012395;

COSMIC: COSV53012395;