rs2297626

Variant names:

• chr13-40659865-T-C
• rs2297626
• NM_002015.4:c.630+5718A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002015.4(FOXO1):​c.630+5718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,096 control chromosomes in the GnomAD database, including 1,992 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 (1992 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.630+5718A>G		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+5718A>G		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
FOXO1	ENST00000655267.1	n.333+5718A>G		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.295+5718A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18478 AN: 151978 Hom.: 1967 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.122 AC: 18560 AN: 152096 Hom.: 1992 Cov.: 32 AF XY: 0.126 AC XY: 9339 AN XY: 74362

African (AFR) AF: 0.250 AC: 10365 AN: 41436

American (AMR) AF: 0.122 AC: 1861 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2040 AN: 5156

South Asian (SAS) AF: 0.118 AC: 568 AN: 4818

European-Finnish (FIN) AF: 0.0939 AC: 995 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2234 AN: 68008

Other (OTH) AF: 0.122 AC: 258 AN: 2112

Alfa AF: 0.0789 Hom.: 109

Bravo AF: 0.131

Asia WGS AF: 0.297 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.50
PhyloP100		0.43
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: rs2297626; hg19: chr13-41234002;