8-21970322-A-G

Variant names:

• chr8-21970322-A-G
• rs4871903
• NM_015024.5:c.426+12A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 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.426+12A>G		intron	N/A	NP_055839.3
	XPO7	NM_001100161.2		c.426+12A>G		intron	N/A	NP_001093631.1
	XPO7	NM_001362802.2		c.426+12A>G		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.426+12A>G		intron	N/A	ENSP00000252512.9
	XPO7	ENST00000518017.1	TSL:1	n.621+12A>G		intron	N/A
	XPO7	ENST00000433566.8	TSL:5	c.429+12A>G		intron	N/A	ENSP00000410249.3

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

GnomAD2 exomes AF: 0.369 AC: 90205 AN: 244348 AF XY: 0.368

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 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

African (AFR) AF: 0.270 AC: 8984 AN: 33284

American (AMR) AF: 0.259 AC: 11392 AN: 43948

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10127 AN: 25976

East Asian (EAS) AF: 0.423 AC: 16765 AN: 39612

South Asian (SAS) AF: 0.197 AC: 16879 AN: 85534

European-Finnish (FIN) AF: 0.447 AC: 23805 AN: 53228

Middle Eastern (MID) AF: 0.335 AC: 1925 AN: 5746

European-Non Finnish (NFE) AF: 0.439 AC: 486851 AN: 1109798

Other (OTH) AF: 0.401 AC: 24127 AN: 60192

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

African (AFR) AF: 0.268 AC: 11078 AN: 41406

American (AMR) AF: 0.289 AC: 4413 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2273 AN: 5154

South Asian (SAS) AF: 0.189 AC: 908 AN: 4816

European-Finnish (FIN) AF: 0.456 AC: 4798 AN: 10514

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

European-Non Finnish (NFE) AF: 0.426 AC: 28948 AN: 67922

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.386 Hom.: 4634

Bravo AF: 0.352

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.52
PhyloP100		-1.1
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)		0.090		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: rs4871903; hg19: chr8-21827833; COSMIC: COSV53012383; COSMIC: COSV53012383;