chr2-61483438-A-C

Variant names:

• chr2-61483438-A-C
• rs11125883
• NM_003400.4:c.2678-347T>G

Variant summary

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

The NM_003400.4(XPO1):​c.2678-347T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 209,252 control chromosomes in the GnomAD database, including 11,770 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 0.31 (8184 hom., cov: 31)
  • Exomes 𝑓: 0.34 (3586 hom.)
• Consequence: XPO1 NM_003400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 14 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO1	NM_003400.4	c.2678-347T>G		intron_variant	Intron 21 of 24	ENST00000401558.7	NP_003391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO1	ENST00000401558.7	c.2678-347T>G		intron_variant	Intron 21 of 24	1	NM_003400.4	ENSP00000384863.2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47128 AN: 151814 Hom.: 8181 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.340 AC: 19499 AN: 57320 Hom.: 3586 Cov.: 0 AF XY: 0.330 AC XY: 9641 AN XY: 29254

African (AFR) AF: 0.151 AC: 169 AN: 1120

American (AMR) AF: 0.304 AC: 627 AN: 2062

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 636 AN: 1644

East Asian (EAS) AF: 0.393 AC: 900 AN: 2290

South Asian (SAS) AF: 0.191 AC: 1059 AN: 5534

European-Finnish (FIN) AF: 0.438 AC: 1185 AN: 2708

Middle Eastern (MID) AF: 0.433 AC: 97 AN: 224

European-Non Finnish (NFE) AF: 0.356 AC: 13581 AN: 38202

Other (OTH) AF: 0.352 AC: 1245 AN: 3536

GnomAD4 genome AF: 0.310 AC: 47142 AN: 151932 Hom.: 8184 Cov.: 31 AF XY: 0.315 AC XY: 23391 AN XY: 74230

African (AFR) AF: 0.155 AC: 6431 AN: 41474

American (AMR) AF: 0.316 AC: 4812 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3466

East Asian (EAS) AF: 0.383 AC: 1977 AN: 5158

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5158 AN: 10534

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25158 AN: 67942

Other (OTH) AF: 0.343 AC: 722 AN: 2108

Alfa AF: 0.347 Hom.: 27333

Bravo AF: 0.293

Asia WGS AF: 0.269 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.38
PhyloP100		-0.46
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: rs11125883; hg19: chr2-61710573;