rs4871903

Positions:

• chr8-21970322-A-G

Variant summary

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

The NM_015024.5(XPO7):​c.426+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,609,164 control chromosomes in the GnomAD database, including 138,269 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 (10514 hom., cov: 31)
  • Exomes 𝑓: 0.41 (127755 hom.)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO7	NM_015024.5	c.426+12A>G		intron_variant		ENST00000252512.14
XPO7	NM_001100161.2	c.426+12A>G		intron_variant
XPO7	NM_001362802.2	c.426+12A>G		intron_variant
XPO7	NR_156173.2	n.535+12A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO7	ENST00000252512.14	c.426+12A>G		intron_variant		1	NM_015024.5	P1
XPO7	ENST00000518017.1	n.621+12A>G		intron_variant, non_coding_transcript_variant		1
XPO7	ENST00000433566.8	c.429+12A>G		intron_variant		5
XPO7	ENST00000521303.5	c.440+12A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55096 AN: 151728 Hom.: 10517 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.369 AC: 90205 AN: 244348 Hom.: 17806 AF XY: 0.368 AC XY: 48851 AN XY: 132620

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.452

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.412 AC: 600855 AN: 1457318 Hom.: 127755 Cov.: 33 AF XY: 0.407 AC XY: 294601 AN XY: 724718

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.363 AC: 55118 AN: 151846 Hom.: 10514 Cov.: 31 AF XY: 0.359 AC XY: 26613 AN XY: 74194

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.375

Alfa AF: 0.383 Hom.: 3012

Bravo AF: 0.352

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4871903; hg19: chr8-21827833; COSMIC: COSV53012383; COSMIC: COSV53012383;