chr6-108627138-T-A

Variant names:

• chr6-108627138-T-A
• rs1935957
• NM_001455.4:c.622-36317T>A

Variant summary

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

The NM_001455.4(FOXO3):​c.622-36317T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,264 control chromosomes in the GnomAD database, including 65,681 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 0.93 (65681 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 2 publications found

Genes affected

FOXO3 (HGNC:3821): (forkhead box O3) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

ENSG00000294744 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001455.4. 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
	FOXO3	NM_001455.4	MANE Select	c.622-36317T>A		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.622-36317T>A		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.121-36317T>A		intron	N/A	NP_001402068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.622-36317T>A		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.622-36317T>A		intron	N/A	ENSP00000339527.6
	ENSG00000294744	ENST00000725671.1		n.453-12355T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141115 AN: 152146 Hom.: 65639 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.942

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

GnomAD4 genome AF: 0.927 AC: 141215 AN: 152264 Hom.: 65681 Cov.: 32 AF XY: 0.922 AC XY: 68621 AN XY: 74446

African (AFR) AF: 0.873 AC: 36286 AN: 41556

American (AMR) AF: 0.959 AC: 14660 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3321 AN: 3470

East Asian (EAS) AF: 0.934 AC: 4830 AN: 5172

South Asian (SAS) AF: 0.783 AC: 3779 AN: 4824

European-Finnish (FIN) AF: 0.882 AC: 9349 AN: 10604

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65829 AN: 68030

Other (OTH) AF: 0.942 AC: 1988 AN: 2110

Alfa AF: 0.945 Hom.: 7920

Bravo AF: 0.934

Asia WGS AF: 0.850 AC: 2955 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.1
DANN	Benign	0.79
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: rs1935957; hg19: chr6-108948341;