Genetic Variant NM_002015.4:c.630+44309C>G (chr13-40621274-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002015.4(FOXO1):c.630+44309C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXO1
NM_002015.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Publications

13 publications found

Variant links:

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]

FOXO1 links:

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

RLIMP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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>G		intron	N/A	NP_002006.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

611786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

323912

African (AFR)

AF:

0.00

AC:

AN:

11884

American (AMR)

AF:

0.00

AC:

AN:

27456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14022

East Asian (EAS)

AF:

0.00

AC:

AN:

13270

South Asian (SAS)

AF:

0.00

AC:

AN:

52482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3550

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

427402

Other (OTH)

AF:

0.00

AC:

AN:

26028

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

3.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over