rs9603776

Variant names:

• chr13-40649749-C-T
• rs9603776
• NM_002015.4:c.630+15834G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.630+15834G>A		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_047430204.1	c.-4492G>A		5_prime_UTR_variant	Exon 1 of 3		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+15834G>A		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
FOXO1	ENST00000655267.1	n.333+15834G>A		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.295+15834G>A		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.00431 AC: 179 AN: 41542

American (AMR) AF: 0.00961 AC: 147 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5188

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4816

European-Finnish (FIN) AF: 0.0224 AC: 237 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1668 AN: 68020

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.0211 Hom.: 123

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
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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: rs9603776; hg19: chr13-41223886;