rs1334241

chr13-40648973-C-T

Variant summary

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

The NM_002015.4(FOXO1):c.630+16610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,116 control chromosomes in the GnomAD database, including 2,990 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 0.19 (2990 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

Genes affected

FOXO1 (HGNC:3819): (forkhead box O1) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.630+16610G>A		intron_variant		ENST00000379561.6
FOXO1	XM_047430204.1	c.-3716G>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+16610G>A		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.333+16610G>A		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.296-15725G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29350 AN: 151998 Hom.: 2986 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.193 AC: 29371 AN: 152116 Hom.: 2990 Cov.: 32 AF XY: 0.197 AC XY: 14631 AN XY: 74354

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0942

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.173

Alfa AF: 0.200 Hom.: 6195

Bravo AF: 0.187

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.63

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: rs1334241; hg19: chr13-41223110; COSMIC: COSV65427875;