13-40572164-T-C

Position:

• chr13-40572164-T-C

Variant summary

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

The NM_002015.4(FOXO1):​c.631-11304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,160 control chromosomes in the GnomAD database, including 2,514 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 0.15 (2514 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ENSG00000288542 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-11304A>G		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-9557A>G		5_prime_UTR_variant	1/3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-11304A>G		intron_variant			XP_011533310.1
FOXO1	XM_047430204.1	c.-81-11304A>G		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-11304A>G		intron_variant		1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.108-11304A>G		intron_variant		5
FOXO1	ENST00000655267.1	n.334-9402A>G		intron_variant
FOXO1	ENST00000660760.1	n.398-11304A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22532 AN: 152042 Hom.: 2497 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.148 AC: 22581 AN: 152160 Hom.: 2514 Cov.: 32 AF XY: 0.153 AC XY: 11367 AN XY: 74386

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.175

Alfa AF: 0.111 Hom.: 2642

Bravo AF: 0.156

Asia WGS AF: 0.423 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.030
DANN	Benign	0.63

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: rs2755213; hg19: chr13-41146301;