chr2-61522555-C-T

Position:

• chr2-61522555-C-T

Variant summary

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

The NM_003400.4(XPO1):​c.301+56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,471,006 control chromosomes in the GnomAD database, including 275,530 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 0.61 (28070 hom., cov: 32)
  • Exomes 𝑓: 0.61 (247460 hom.)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO1	NM_003400.4	c.301+56G>A		intron_variant		ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.301+56G>A		intron_variant		1	NM_003400.4	ENSP00000384863	P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92164 AN: 151966 Hom.: 28052 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.611 AC: 806052 AN: 1318922 Hom.: 247460 AF XY: 0.612 AC XY: 405425 AN XY: 662418

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.606 AC: 92237 AN: 152084 Hom.: 28070 Cov.: 32 AF XY: 0.607 AC XY: 45133 AN XY: 74342

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.632

Alfa AF: 0.608 Hom.: 26926

Bravo AF: 0.605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.6
DANN	Benign	0.67
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.9

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: rs3732171; hg19: chr2-61749690; COSMIC: COSV68944410; COSMIC: COSV68944410;