13-40622740-T-C

Variant names:

• chr13-40622740-T-C
• rs12876443
• NM_002015.4:c.630+42843A>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+42843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 152,304 control chromosomes in the GnomAD database, including 527 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 0.071 (527 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.630+42843A>G		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535008.3	c.-8504A>G		5_prime_UTR_variant	Exon 1 of 3		XP_011533310.1
FOXO1	XM_047430204.1	c.-82+22599A>G		intron_variant	Intron 1 of 2		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+42843A>G		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
FOXO1	ENST00000655267.1	n.333+42843A>G		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.397+10407A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10861 AN: 152186 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0713 AC: 10855 AN: 152304 Hom.: 527 Cov.: 32 AF XY: 0.0689 AC XY: 5131 AN XY: 74472

African (AFR) AF: 0.0181 AC: 751 AN: 41564

American (AMR) AF: 0.0613 AC: 937 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3468

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5190

South Asian (SAS) AF: 0.130 AC: 630 AN: 4832

European-Finnish (FIN) AF: 0.0538 AC: 570 AN: 10604

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7142 AN: 68032

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0991 Hom.: 425

Bravo AF: 0.0687

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.56
PhyloP100		-0.34
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: rs12876443; hg19: chr13-41196877;