8-21969651-C-T

Position:

• chr8-21969651-C-T

Variant summary

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

The NM_015024.5(XPO7):​c.259+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,323,732 control chromosomes in the GnomAD database, including 111,543 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 (10581 hom., cov: 32)
  • Exomes 𝑓: 0.41 (100962 hom.)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO7	NM_015024.5	c.259+75C>T		intron_variant		ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.259+75C>T		intron_variant			NP_001093631.1
XPO7	NM_001362802.2	c.259+75C>T		intron_variant			NP_001349731.1
XPO7	NR_156173.2	n.368+75C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.259+75C>T		intron_variant		1	NM_015024.5	ENSP00000252512.9

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55402 AN: 151838 Hom.: 10578 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.407 AC: 477072 AN: 1171776 Hom.: 100962 Cov.: 15 AF XY: 0.401 AC XY: 236051 AN XY: 588682

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.365 AC: 55427 AN: 151956 Hom.: 10581 Cov.: 32 AF XY: 0.360 AC XY: 26760 AN XY: 74256

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.372

Alfa AF: 0.381 Hom.: 2327

Bravo AF: 0.351

Asia WGS AF: 0.331 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2291317; hg19: chr8-21827162; COSMIC: COSV53011848; COSMIC: COSV53011848;