13-40599271-G-C

Position:

• chr13-40599271-G-C

Variant summary

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

The ENST00000379561.6(FOXO1):​c.631-38411C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 150,744 control chromosomes in the GnomAD database, including 2,510 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 0.17 (2510 hom., cov: 31)
• Consequence: FOXO1 ENST00000379561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-38411C>G		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-36664C>G		5_prime_UTR_variant	1/3		XP_011533312.1
FOXO1	XM_011535008.3	c.87+14879C>G		intron_variant			XP_011533310.1
FOXO1	XM_047430204.1	c.-81-38411C>G		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-38411C>G		intron_variant		1	NM_002015.4	ENSP00000368880	P1
FOXO1	ENST00000655267.1	n.334-36509C>G		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.397+33876C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25688 AN: 150682 Hom.: 2508 Cov.: 31

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.170 AC: 25692 AN: 150744 Hom.: 2510 Cov.: 31 AF XY: 0.175 AC XY: 12902 AN XY: 73528

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.156

Alfa AF: 0.193 Hom.: 421

Bravo AF: 0.160

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.33

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: rs4943794; hg19: chr13-41173408;