rs4503258

Variant names:

• chrX-71103387-C-T
• rs4503258
• NM_005938.4:c.*1303C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO4	NM_005938.4	MANE Select	c.*1303C>T		3_prime_UTR	Exon 3 of 3	NP_005929.2
	FOXO4	NM_001170931.2		c.*1303C>T		3_prime_UTR	Exon 4 of 4	NP_001164402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO4	ENST00000374259.8	TSL:1 MANE Select	c.*1303C>T		3_prime_UTR	Exon 3 of 3	ENSP00000363377.3
	FOXO4	ENST00000341558.4	TSL:5	c.*1303C>T		3_prime_UTR	Exon 4 of 4	ENSP00000342209.3

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 4199 AN: 110200 Hom.: 234 Cov.: 21

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

African (AFR) AF: 0.00824 AC: 20 AN: 2427

American (AMR) AF: 0.248 AC: 404 AN: 1629

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 60 AN: 2968

East Asian (EAS) AF: 0.0532 AC: 409 AN: 7683

South Asian (SAS) AF: 0.115 AC: 46 AN: 399

European-Finnish (FIN) AF: 0.00289 AC: 1 AN: 346

Middle Eastern (MID) AF: 0.00743 AC: 2 AN: 269

European-Non Finnish (NFE) AF: 0.0177 AC: 558 AN: 31579

Other (OTH) AF: 0.0437 AC: 195 AN: 4462

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

African (AFR) AF: 0.00662 AC: 201 AN: 30346

American (AMR) AF: 0.222 AC: 2288 AN: 10292

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 48 AN: 2632

East Asian (EAS) AF: 0.0725 AC: 249 AN: 3435

South Asian (SAS) AF: 0.0834 AC: 212 AN: 2543

European-Finnish (FIN) AF: 0.00571 AC: 34 AN: 5955

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.0205 AC: 1077 AN: 52642

Other (OTH) AF: 0.0635 AC: 96 AN: 1511

Alfa AF: 0.0474 Hom.: 732

Bravo AF: 0.0581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs4503258; hg19: chrX-70323237;