2-61476721-A-G

Variant names:

• chr2-61476721-A-G
• rs4430924
• ENST00000677110.1:n.5882T>C

Variant summary

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

The ENST00000677110.1(XPO1):​n.5882T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,092 control chromosomes in the GnomAD database, including 34,647 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 0.67 (34647 hom., cov: 32)
• Consequence: XPO1 ENST00000677110.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• 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]

USP34-DT (HGNC:55262): (USP34 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34-DT	NR_185882.1	n.285-3604A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000677110.1	n.5882T>C		non_coding_transcript_exon_variant	Exon 22 of 22
XPO1	ENST00000678113.1	n.8241T>C		non_coding_transcript_exon_variant	Exon 16 of 16
USP34-DT	ENST00000578974.3	n.171+4913A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101918 AN: 151974 Hom.: 34604 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.671 AC: 102018 AN: 152092 Hom.: 34647 Cov.: 32 AF XY: 0.672 AC XY: 49991 AN XY: 74346

African (AFR) AF: 0.786 AC: 32613 AN: 41500

American (AMR) AF: 0.609 AC: 9304 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2354 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3299 AN: 5174

South Asian (SAS) AF: 0.615 AC: 2962 AN: 4816

European-Finnish (FIN) AF: 0.674 AC: 7128 AN: 10580

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42044 AN: 67970

Other (OTH) AF: 0.684 AC: 1445 AN: 2112

Alfa AF: 0.635 Hom.: 117944

Bravo AF: 0.672

Asia WGS AF: 0.634 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4430924; hg19: chr2-61703856;