rs2984121

Variant names:

• chr13-40587842-C-G
• rs2984121
• NM_002015.4:c.631-26982G>C

Variant summary

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

The NM_002015.4(FOXO1):​c.631-26982G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,230 control chromosomes in the GnomAD database, including 1,487 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 (1487 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 7 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]

ENSG00000288542 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-26982G>C		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-25235G>C		5_prime_UTR_variant	Exon 1 of 3		XP_011533312.1
FOXO1	XM_011535008.3	c.87+26308G>C		intron_variant	Intron 1 of 2		XP_011533310.1
FOXO1	XM_047430204.1	c.-81-26982G>C		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.631-26982G>C		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.107+23179G>C		intron_variant	Intron 1 of 3	5
FOXO1	ENST00000655267.1	n.334-25080G>C		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.398-26982G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18019 AN: 152112 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.118 AC: 18004 AN: 152230 Hom.: 1487 Cov.: 32 AF XY: 0.118 AC XY: 8798 AN XY: 74426

African (AFR) AF: 0.0278 AC: 1153 AN: 41546

American (AMR) AF: 0.108 AC: 1648 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0532 AC: 257 AN: 4832

European-Finnish (FIN) AF: 0.183 AC: 1936 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11925 AN: 67996

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.145 Hom.: 250

Bravo AF: 0.109

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		0.15
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: rs2984121; hg19: chr13-41161979; COSMIC: COSV65428364;