2-61508434-C-T

Variant names:

• chr2-61508434-C-T
• rs766447
• NM_003400.4:c.302-6124G>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.302-6124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,980 control chromosomes in the GnomAD database, including 28,529 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 (28529 hom., cov: 32)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO1	NM_003400.4	c.302-6124G>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.302-6124G>A		intron_variant	Intron 4 of 24	1	NM_003400.4	ENSP00000384863.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92944 AN: 151862 Hom.: 28502 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.612 AC: 93027 AN: 151980 Hom.: 28529 Cov.: 32 AF XY: 0.613 AC XY: 45505 AN XY: 74274

African (AFR) AF: 0.627 AC: 25966 AN: 41434

American (AMR) AF: 0.576 AC: 8796 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3355 AN: 5162

South Asian (SAS) AF: 0.610 AC: 2946 AN: 4832

European-Finnish (FIN) AF: 0.600 AC: 6320 AN: 10530

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41141 AN: 67972

Other (OTH) AF: 0.633 AC: 1333 AN: 2106

Alfa AF: 0.597 Hom.: 3826

Bravo AF: 0.611

Asia WGS AF: 0.622 AC: 2164 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.038
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: rs766447; hg19: chr2-61735569;