rs3816786

Variant names:

• chr8-22002914-T-A
• rs3816786
• NM_015024.5:c.2944-305T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22002914-T-A
• chr8-22002914-T-C
• chr8-22002914-T-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.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
• Publications: 3 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

ENSG00000295189 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XPO7	NM_015024.5	c.2944-305T>A		intron_variant	Intron 25 of 27	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.2971-305T>A		intron_variant	Intron 25 of 27		NP_001093631.1
XPO7	NM_001362802.2	c.2878-305T>A		intron_variant	Intron 24 of 26		NP_001349731.1
XPO7	NR_156173.2	n.3164-305T>A		intron_variant	Intron 26 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.2944-305T>A		intron_variant	Intron 25 of 27	1	NM_015024.5	ENSP00000252512.9
XPO7	ENST00000433566.8	c.2947-305T>A		intron_variant	Intron 25 of 27	5		ENSP00000410249.3
ENSG00000295189	ENST00000728549.1	n.511-24A>T		intron_variant	Intron 1 of 2
XPO7	ENST00000522015.1	n.-71T>A		upstream_gene_variant		3

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

African (AFR) AF: 0.240 AC: 344 AN: 1434

American (AMR) AF: 0.280 AC: 785 AN: 2806

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 761 AN: 2028

East Asian (EAS) AF: 0.403 AC: 1147 AN: 2848

South Asian (SAS) AF: 0.181 AC: 1379 AN: 7622

European-Finnish (FIN) AF: 0.441 AC: 1552 AN: 3516

Middle Eastern (MID) AF: 0.349 AC: 113 AN: 324

European-Non Finnish (NFE) AF: 0.428 AC: 17183 AN: 40160

Other (OTH) AF: 0.404 AC: 1610 AN: 3982

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

African (AFR) AF: 0.262 AC: 10869 AN: 41488

American (AMR) AF: 0.289 AC: 4407 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2239 AN: 5168

South Asian (SAS) AF: 0.187 AC: 901 AN: 4810

European-Finnish (FIN) AF: 0.458 AC: 4837 AN: 10560

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28745 AN: 67944

Other (OTH) AF: 0.373 AC: 788 AN: 2110

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs3816786; hg19: chr8-21860425;