rs9603776

chr13-40649749-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002015.4(FOXO1):c.630+15834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,254 control chromosomes in the GnomAD database, including 33 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 0.016 (33 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2374/152254) while in subpopulation NFE AF= 0.0245 (1668/68020). AF 95% confidence interval is 0.0235. There are 33 homozygotes in gnomad4. There are 1150 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.630+15834G>A		intron_variant		ENST00000379561.6
FOXO1	XM_047430204.1	c.-4492G>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+15834G>A		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.333+15834G>A		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.295+15834G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2374 AN: 152136 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00968

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0101

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

GnomAD4 genome AF: 0.0156 AC: 2374 AN: 152254 Hom.: 33 Cov.: 32 AF XY: 0.0154 AC XY: 1150 AN XY: 74448

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.00961

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.0207 Hom.: 49

Bravo AF: 0.0148

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.9
Dann	Benign	0.61

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: rs9603776; hg19: chr13-41223886;