rs12854161

Positions:

• chr13-40628247-G-A

Variant summary

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

The NM_002015.4(FOXO1):​c.630+37336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,644 control chromosomes in the GnomAD database, including 3,261 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 0.20 (3261 hom., cov: 30)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.630+37336C>T		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_047430204.1	c.-82+17092C>T		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+37336C>T		intron_variant		1	NM_002015.4	ENSP00000368880	P1
FOXO1	ENST00000655267.1	n.333+37336C>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.397+4900C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29881 AN: 151524 Hom.: 3259 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.197 AC: 29881 AN: 151644 Hom.: 3261 Cov.: 30 AF XY: 0.193 AC XY: 14292 AN XY: 74066

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.187

Alfa AF: 0.238 Hom.: 7439

Bravo AF: 0.187

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.79

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: rs12854161; hg19: chr13-41202384;