rs4770073

Positions:

• chr13-20807978-A-G

Variant summary

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

The NM_022459.5(XPO4):​c.1640-344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,208 control chromosomes in the GnomAD database, including 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 0.079 (977 hom., cov: 32)
• Consequence: XPO4 NM_022459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

Genes affected

XPO4 (HGNC:17796): (exportin 4) XPO4 belongs to a large family of karyopherins (see MIM 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments (Lipowsky et al., 2000 [PubMed 10944119]).[supplied by OMIM, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO4	NM_022459.5	c.1640-344T>C		intron_variant		ENST00000255305.11	NP_071904.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO4	ENST00000255305.11	c.1640-344T>C		intron_variant		1	NM_022459.5	ENSP00000255305	P1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12064 AN: 152090 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0793 AC: 12064 AN: 152208 Hom.: 977 Cov.: 32 AF XY: 0.0833 AC XY: 6202 AN XY: 74420

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0768 Hom.: 254

Bravo AF: 0.0888

Asia WGS AF: 0.228 AC: 792 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.81

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: rs4770073; hg19: chr13-21382117;