chr8-21978873-C-G

Variant names:

• chr8-21978873-C-G
• rs1809498
• NM_015024.5:c.837+1030C>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.837+1030C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,022 control chromosomes in the GnomAD database, including 10,956 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 0.37 (10956 hom., cov: 32)
• Consequence: XPO7 NM_015024.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	NM_015024.5	MANE Select	c.837+1030C>G		intron	N/A	NP_055839.3
	XPO7	NM_001100161.2		c.864+1030C>G		intron	N/A	NP_001093631.1
	XPO7	NM_001362802.2		c.771+1030C>G		intron	N/A	NP_001349731.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO7	ENST00000252512.14	TSL:1 MANE Select	c.837+1030C>G		intron	N/A	ENSP00000252512.9	Q9UIA9
	XPO7	ENST00000433566.8	TSL:5	c.840+1030C>G		intron	N/A	ENSP00000410249.3	E7ESC6
	XPO7	ENST00000879832.1		c.837+1030C>G		intron	N/A	ENSP00000549891.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55996 AN: 151902 Hom.: 10956 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 56015 AN: 152022 Hom.: 10956 Cov.: 32 AF XY: 0.364 AC XY: 27060 AN XY: 74294

African (AFR) AF: 0.264 AC: 10947 AN: 41448

American (AMR) AF: 0.263 AC: 4021 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2090 AN: 5172

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4824

European-Finnish (FIN) AF: 0.469 AC: 4951 AN: 10558

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30213 AN: 67952

Other (OTH) AF: 0.379 AC: 802 AN: 2114

Alfa AF: 0.413 Hom.: 1645

Bravo AF: 0.352

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		-0.15
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: rs1809498; hg19: chr8-21836384;