chr13-40565907-T-A

Variant names:

• chr13-40565907-T-A
• rs2180961
• NM_002015.4:c.631-5047A>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.631-5047A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,258 control chromosomes in the GnomAD database, including 1,585 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 0.13 (1585 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.631-5047A>T		intron	N/A	NP_002006.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.631-5047A>T		intron	N/A	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.631-5047A>T		intron	N/A	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.631-5047A>T		intron	N/A	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20473 AN: 152140 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.135 AC: 20480 AN: 152258 Hom.: 1585 Cov.: 32 AF XY: 0.139 AC XY: 10320 AN XY: 74442

African (AFR) AF: 0.0679 AC: 2819 AN: 41536

American (AMR) AF: 0.183 AC: 2803 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.0912 AC: 473 AN: 5188

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1667 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10505 AN: 68026

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.147 Hom.: 215

Bravo AF: 0.131

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.087
PhyloP100		-0.26
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: rs2180961; hg19: chr13-41140044;