chr13-40557795-C-T

Position:

• chr13-40557795-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002015.4(FOXO1):​c.*1254G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,276 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (521 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FOXO1 NM_002015.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.437

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-40557795-C-T is Benign according to our data. Variant chr13-40557795-C-T is described in ClinVar as [Benign]. Clinvar id is 1291640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.*1254G>A		3_prime_UTR_variant	3/3	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535008.3	c.*1254G>A		3_prime_UTR_variant	3/3		XP_011533310.1
FOXO1	XM_011535010.3	c.*1254G>A		3_prime_UTR_variant	3/3		XP_011533312.1
FOXO1	XM_047430204.1	c.*1254G>A		3_prime_UTR_variant	3/3		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.*1254G>A		3_prime_UTR_variant	3/3	1	NM_002015.4	ENSP00000368880	P1

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6385 AN: 152158 Hom.: 508 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0487

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0422 AC: 6420 AN: 152276 Hom.: 521 Cov.: 33 AF XY: 0.0485 AC XY: 3607 AN XY: 74440

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.0910

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0233 Hom.: 114

Bravo AF: 0.0413

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2020	This variant is associated with the following publications: (PMID: 25739100) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.27

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: rs17592236; hg19: chr13-41131932;