rs12583418

Positions:

• chr13-40621274-G-A
• chr13-40621274-G-C

Variant summary

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

The ENST00000379561.6(FOXO1):​c.630+44309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 755,212 control chromosomes in the GnomAD database, including 43,153 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 0.41 (13843 hom., cov: 31)
  • Exomes 𝑓: 0.28 (29310 hom.)
• Consequence: FOXO1 ENST00000379561.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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]

RLIMP1 (HGNC:39682): (ring finger protein, LIM domain interacting pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.630+44309C>T		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_011535008.3	c.-7038C>T		5_prime_UTR_variant	1/3		XP_011533310.1
FOXO1	XM_047430204.1	c.-82+24065C>T		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+44309C>T		intron_variant		1	NM_002015.4	ENSP00000368880	P1
RLIMP1	ENST00000339626.5	n.1606G>A		non_coding_transcript_exon_variant	3/3
FOXO1	ENST00000655267.1	n.333+44309C>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.397+11873C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62034 AN: 151866 Hom.: 13798 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.282 AC: 169978 AN: 603226 Hom.: 29310 Cov.: 8 AF XY: 0.293 AC XY: 93688 AN XY: 319668

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.638

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.409 AC: 62144 AN: 151986 Hom.: 13843 Cov.: 31 AF XY: 0.414 AC XY: 30790 AN XY: 74304

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.403

Alfa AF: 0.339 Hom.: 3900

Bravo AF: 0.417

Asia WGS AF: 0.641 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.4
DANN	Benign	0.74

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: rs12583418; hg19: chr13-41195411;