8-21999756-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015024.5(XPO7):​c.2782+82G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,408,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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>T		intron	N/A	NP_055839.3
	XPO7	NM_001100161.2		c.2809+82G>T		intron	N/A	NP_001093631.1
	XPO7	NM_001362802.2		c.2716+82G>T		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>T		intron	N/A	ENSP00000252512.9
	XPO7	ENST00000433566.8	TSL:5	c.2785+82G>T		intron	N/A	ENSP00000410249.3
	XPO7	ENST00000517551.2	TSL:5	c.*82G>T		downstream_gene	N/A	ENSP00000429317.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000497 AC: 7 AN: 1408206 Hom.: 0 AF XY: 0.00000860 AC XY: 6 AN XY: 697586

African (AFR) AF: 0.00 AC: 0 AN: 32480

American (AMR) AF: 0.00 AC: 0 AN: 39120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39064

South Asian (SAS) AF: 0.00 AC: 0 AN: 79890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00000649 AC: 7 AN: 1078418

Other (OTH) AF: 0.00 AC: 0 AN: 58448

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.78
PhyloP100		-1.6

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;