rs3816786

Positions:

• chr8-22002914-T-A
• chr8-22002914-T-C
• chr8-22002914-T-G

Variant summary

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

The NM_015024.5(XPO7):​c.2944-305T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 216,744 control chromosomes in the GnomAD database, including 15,522 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 (10348 hom., cov: 32)
  • Exomes 𝑓: 0.38 (5174 hom.)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO7	NM_015024.5	c.2944-305T>A		intron_variant		ENST00000252512.14
XPO7	NM_001100161.2	c.2971-305T>A		intron_variant
XPO7	NM_001362802.2	c.2878-305T>A		intron_variant
XPO7	NR_156173.2	n.3164-305T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO7	ENST00000252512.14	c.2944-305T>A		intron_variant		1	NM_015024.5	P1
XPO7	ENST00000433566.8	c.2947-305T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54667 AN: 151904 Hom.: 10350 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.384 AC: 24874 AN: 64720 Hom.: 5174 AF XY: 0.370 AC XY: 12570 AN XY: 33946

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.360 AC: 54691 AN: 152024 Hom.: 10348 Cov.: 32 AF XY: 0.356 AC XY: 26452 AN XY: 74318

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.373

Alfa AF: 0.397 Hom.: 1498

Bravo AF: 0.348

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.72

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: rs3816786; hg19: chr8-21860425;