X-71103387-C-T

Position:

• chrX-71103387-C-T

Variant summary

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

The NM_005938.4(FOXO4):​c.*1303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 162,009 control chromosomes in the GnomAD database, including 313 homozygotes. There are 1,687 hemizygotes in GnomAD. 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 0.038 (237 hom., 1315 hem., cov: 21)
  • Exomes 𝑓: 0.033 (76 hom. 372 hem.)
• Consequence: FOXO4 NM_005938.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

Genes affected

FOXO4 (HGNC:7139): (forkhead box O4) This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO4	NM_005938.4	c.*1303C>T		3_prime_UTR_variant	3/3	ENST00000374259.8	NP_005929.2
FOXO4	NM_001170931.2	c.*1303C>T		3_prime_UTR_variant	4/4		NP_001164402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO4	ENST00000374259.8	c.*1303C>T		3_prime_UTR_variant	3/3	1	NM_005938.4	ENSP00000363377.3

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 4199 AN: 110200 Hom.: 234 Cov.: 21 AF XY: 0.0404 AC XY: 1310 AN XY: 32462

Gnomad AFR AF: 0.00664

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.00571

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0616

GnomAD4 exome AF: 0.0327 AC: 1695 AN: 51762 Hom.: 76 Cov.: 0 AF XY: 0.0305 AC XY: 372 AN XY: 12190

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0532

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.00289

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0437

GnomAD4 genome AF: 0.0382 AC: 4206 AN: 110247 Hom.: 237 Cov.: 21 AF XY: 0.0404 AC XY: 1315 AN XY: 32519

Gnomad4 AFR AF: 0.00662

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.00571

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0483 Hom.: 667

Bravo AF: 0.0581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4503258; hg19: chrX-70323237;