rs1050567

Positions:

• chr2-61478528-C-T

Variant summary

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

The ENST00000401558.7(XPO1):​c.*292G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 332,782 control chromosomes in the GnomAD database, including 3,414 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 0.11 (1294 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2120 hom.)
• Consequence: XPO1 ENST00000401558.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

XPO1 (HGNC:12825): (exportin 1) This cell-cycle-regulated gene encodes a protein that mediates leucine-rich nuclear export signal (NES)-dependent protein transport. The protein specifically inhibits the nuclear export of Rev and U snRNAs. It is involved in the control of several cellular processes by controlling the localization of cyclin B, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1. [provided by RefSeq, Jan 2015]

USP34-DT (HGNC:55262): (USP34 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO1	NM_003400.4	c.*292G>A		3_prime_UTR_variant	25/25	ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.*292G>A		3_prime_UTR_variant	25/25	1	NM_003400.4	ENSP00000384863	P1
USP34-DT	ENST00000692738.1	n.439-4099C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16888 AN: 151930 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.134 AC: 24305 AN: 180734 Hom.: 2120 Cov.: 2 AF XY: 0.137 AC XY: 12407 AN XY: 90424

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.0838

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.111 AC: 16872 AN: 152048 Hom.: 1294 Cov.: 32 AF XY: 0.117 AC XY: 8669 AN XY: 74310

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.0878

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.124

Alfa AF: 0.126 Hom.: 726

Bravo AF: 0.112

Asia WGS AF: 0.288 AC: 1002 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.36
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1050567; hg19: chr2-61705663;