chr13-40621274-G-A

Variant names:

• chr13-40621274-G-A
• rs12583418
• NM_002015.4:c.630+44309C>T

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+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 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 13 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002015.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.630+44309C>T		intron	N/A	NP_002006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.630+44309C>T		intron	N/A	ENSP00000368880.4
	RLIMP1	ENST00000339626.5	TSL:6	n.1606G>A		non_coding_transcript_exon	Exon 3 of 3
	FOXO1	ENST00000655267.1		n.333+44309C>T		intron	N/A

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

African (AFR) AF: 0.473 AC: 5496 AN: 11626

American (AMR) AF: 0.455 AC: 12398 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 3340 AN: 13864

East Asian (EAS) AF: 0.638 AC: 8333 AN: 13052

South Asian (SAS) AF: 0.477 AC: 24901 AN: 52156

European-Finnish (FIN) AF: 0.320 AC: 11314 AN: 35302

Middle Eastern (MID) AF: 0.284 AC: 998 AN: 3518

European-Non Finnish (NFE) AF: 0.228 AC: 95852 AN: 420798

Other (OTH) AF: 0.287 AC: 7346 AN: 25638

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

African (AFR) AF: 0.551 AC: 22815 AN: 41444

American (AMR) AF: 0.411 AC: 6273 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1020 AN: 3462

East Asian (EAS) AF: 0.731 AC: 3775 AN: 5162

South Asian (SAS) AF: 0.515 AC: 2484 AN: 4824

European-Finnish (FIN) AF: 0.358 AC: 3786 AN: 10562

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20795 AN: 67950

Other (OTH) AF: 0.403 AC: 850 AN: 2108

Alfa AF: 0.339 Hom.: 4415

Bravo AF: 0.417

Asia WGS AF: 0.641 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		3.0
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: rs12583418; hg19: chr13-41195411;