rs2180961

Positions:

• chr13-40565907-T-A

Variant summary

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

The NM_002015.4(FOXO1):​c.631-5047A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,258 control chromosomes in the GnomAD database, including 1,585 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 0.13 (1585 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.631-5047A>T		intron_variant		ENST00000379561.6
FOXO1	XM_011535010.3	c.-3300A>T		5_prime_UTR_variant	1/3
FOXO1	XM_011535008.3	c.88-5047A>T		intron_variant
FOXO1	XM_047430204.1	c.-81-5047A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-5047A>T		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.334-3145A>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.398-5047A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20473 AN: 152140 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.135 AC: 20480 AN: 152258 Hom.: 1585 Cov.: 32 AF XY: 0.139 AC XY: 10320 AN XY: 74442

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.128

Alfa AF: 0.147 Hom.: 215

Bravo AF: 0.131

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.087

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: rs2180961; hg19: chr13-41140044;