2-61530586-G-T

Variant names:

• chr2-61530586-G-T
• rs10186325
• NM_003400.4:c.126+3186C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000401558.7(XPO1):​c.126+3186C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,748 control chromosomes in the GnomAD database, including 27,228 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 0.60 (27228 hom., cov: 30)
• Consequence: XPO1 ENST00000401558.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401558.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO1	NM_003400.4	MANE Select	c.126+3186C>A		intron	N/A	NP_003391.1
	XPO1	NM_001410799.1		c.126+3186C>A		intron	N/A	NP_001397728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO1	ENST00000401558.7	TSL:1 MANE Select	c.126+3186C>A		intron	N/A	ENSP00000384863.2
	XPO1	ENST00000406957.5	TSL:1	c.126+3186C>A		intron	N/A	ENSP00000385559.1
	XPO1	ENST00000404992.6	TSL:2	c.126+3186C>A		intron	N/A	ENSP00000385942.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90707 AN: 151632 Hom.: 27211 Cov.: 30

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.598 AC: 90777 AN: 151748 Hom.: 27228 Cov.: 30 AF XY: 0.599 AC XY: 44393 AN XY: 74156

African (AFR) AF: 0.589 AC: 24375 AN: 41368

American (AMR) AF: 0.573 AC: 8726 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2335 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2872 AN: 5146

South Asian (SAS) AF: 0.606 AC: 2920 AN: 4816

European-Finnish (FIN) AF: 0.602 AC: 6323 AN: 10512

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41075 AN: 67894

Other (OTH) AF: 0.628 AC: 1321 AN: 2104

Alfa AF: 0.605 Hom.: 63931

Bravo AF: 0.596

Asia WGS AF: 0.588 AC: 2043 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.17
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: rs10186325; hg19: chr2-61757721;