2-61514676-T-C

Position:

• chr2-61514676-T-C

Variant summary

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

The NM_003400.4(XPO1):​c.301+7935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,424 control chromosomes in the GnomAD database, including 26,977 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 (26977 hom., cov: 29)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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]

XPO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO1	NM_003400.4	c.301+7935A>G		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+7935A>G		intron_variant		1	NM_003400.4	ENSP00000384863.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90246 AN: 151306 Hom.: 26955 Cov.: 29

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.596 AC: 90318 AN: 151424 Hom.: 26977 Cov.: 29 AF XY: 0.598 AC XY: 44250 AN XY: 73986

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.618

Alfa AF: 0.511 Hom.: 2352

Bravo AF: 0.593

Asia WGS AF: 0.616 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.82
DANN	Benign	0.43

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: rs7563678; hg19: chr2-61741811;