rs1809498

Positions:

• chr8-21978873-C-G
• chr8-21978873-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO7	NM_015024.5	c.837+1030C>G		intron_variant		ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.864+1030C>G		intron_variant			NP_001093631.1
XPO7	NM_001362802.2	c.771+1030C>G		intron_variant			NP_001349731.1
XPO7	NR_156173.2	n.946+1030C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.837+1030C>G		intron_variant		1	NM_015024.5	ENSP00000252512	P1
XPO7	ENST00000433566.8	c.840+1030C>G		intron_variant		5		ENSP00000410249

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

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.379

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.69

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: rs1809498; hg19: chr8-21836384;