rs2984121

chr13-40587842-C-G

Variant summary

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

The NM_002015.4(FOXO1):c.631-26982G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,230 control chromosomes in the GnomAD database, including 1,487 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 0.12 (1487 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.631-26982G>C		intron_variant		ENST00000379561.6
FOXO1	XM_011535010.3	c.-25235G>C		5_prime_UTR_variant	1/3
FOXO1	XM_011535008.3	c.87+26308G>C		intron_variant
FOXO1	XM_047430204.1	c.-81-26982G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-26982G>C		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.334-25080G>C		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.398-26982G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18019 AN: 152112 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.118 AC: 18004 AN: 152230 Hom.: 1487 Cov.: 32 AF XY: 0.118 AC XY: 8798 AN XY: 74426

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0532

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.126

Alfa AF: 0.145 Hom.: 250

Bravo AF: 0.109

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.3
Dann	Benign	0.60

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: rs2984121; hg19: chr13-41161979; COSMIC: COSV65428364;