rs17616085

Variant names:

• chr8-21999756-G-A
• rs17616085
• NM_015024.5:c.2782+82G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-21999756-G-A
• chr8-21999756-G-C
• chr8-21999756-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015024.5(XPO7):​c.2782+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,558,982 control chromosomes in the GnomAD database, including 131,481 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 (10265 hom., cov: 32)
  • Exomes 𝑓: 0.41 (121216 hom.)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	NM_015024.5	MANE Select	c.2782+82G>A		intron	N/A	NP_055839.3
	XPO7	NM_001100161.2		c.2809+82G>A		intron	N/A	NP_001093631.1
	XPO7	NM_001362802.2		c.2716+82G>A		intron	N/A	NP_001349731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	ENST00000252512.14	TSL:1 MANE Select	c.2782+82G>A		intron	N/A	ENSP00000252512.9
	XPO7	ENST00000433566.8	TSL:5	c.2785+82G>A		intron	N/A	ENSP00000410249.3
	XPO7	ENST00000517551.2	TSL:5	c.*82G>A		downstream_gene	N/A	ENSP00000429317.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54487 AN: 151942 Hom.: 10268 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.409 AC: 575193 AN: 1406922 Hom.: 121216 AF XY: 0.403 AC XY: 280949 AN XY: 696928

African (AFR) AF: 0.263 AC: 8533 AN: 32460

American (AMR) AF: 0.256 AC: 10012 AN: 39072

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 9248 AN: 24066

East Asian (EAS) AF: 0.418 AC: 16320 AN: 39042

South Asian (SAS) AF: 0.194 AC: 15472 AN: 79850

European-Finnish (FIN) AF: 0.445 AC: 22781 AN: 51160

Middle Eastern (MID) AF: 0.331 AC: 1808 AN: 5464

European-Non Finnish (NFE) AF: 0.434 AC: 467842 AN: 1077402

Other (OTH) AF: 0.397 AC: 23177 AN: 58406

GnomAD4 genome AF: 0.358 AC: 54510 AN: 152060 Hom.: 10265 Cov.: 32 AF XY: 0.355 AC XY: 26360 AN XY: 74316

African (AFR) AF: 0.262 AC: 10857 AN: 41466

American (AMR) AF: 0.288 AC: 4395 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2247 AN: 5178

South Asian (SAS) AF: 0.188 AC: 908 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4813 AN: 10558

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28607 AN: 67974

Other (OTH) AF: 0.371 AC: 785 AN: 2114

Alfa AF: 0.377 Hom.: 1874

Bravo AF: 0.347

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17616085; hg19: chr8-21857267; COSMIC: COSV53012464; COSMIC: COSV53012464;