2-61522555-C-T

Variant names:

• chr2-61522555-C-T
• rs3732171
• NM_003400.4:c.301+56G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XPO1	NM_003400.4	c.301+56G>A		intron_variant	Intron 4 of 24	ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.301+56G>A		intron_variant	Intron 4 of 24	1	NM_003400.4	ENSP00000384863.2

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

African (AFR) AF: 0.599 AC: 18000 AN: 30064

American (AMR) AF: 0.575 AC: 24683 AN: 42918

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17076 AN: 24904

East Asian (EAS) AF: 0.659 AC: 25455 AN: 38604

South Asian (SAS) AF: 0.608 AC: 49692 AN: 81716

European-Finnish (FIN) AF: 0.601 AC: 31178 AN: 51844

Middle Eastern (MID) AF: 0.703 AC: 3840 AN: 5464

European-Non Finnish (NFE) AF: 0.609 AC: 601558 AN: 988058

Other (OTH) AF: 0.625 AC: 34570 AN: 55350

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

African (AFR) AF: 0.595 AC: 24698 AN: 41498

American (AMR) AF: 0.575 AC: 8776 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3366 AN: 5180

South Asian (SAS) AF: 0.612 AC: 2948 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6371 AN: 10560

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41573 AN: 67972

Other (OTH) AF: 0.632 AC: 1332 AN: 2108

Alfa AF: 0.606 Hom.: 35201

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
PhyloP100		0.095
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.9
Mutation Taster		=27/73	disease causing

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