1-41374150-G-T

Position:

• chr1-41374150-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291281.3(FOXO6):​c.415-7466G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,132 control chromosomes in the GnomAD database, including 5,919 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 0.26 (5919 hom., cov: 32)
• Consequence: FOXO6 NM_001291281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

Genes affected

FOXO6 (HGNC:24814): (forkhead box O6) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of dendritic spine development and regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO6	NM_001291281.3	c.415-7466G>T		intron_variant		ENST00000643531.4	NP_001278210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO6	ENST00000641094.2	c.415-7466G>T		intron_variant				ENSP00000493184	P1
FOXO6	ENST00000686812.1	c.30+7375G>T		intron_variant				ENSP00000509631
FOXO6	ENST00000372591.1	n.424-7466G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40215 AN: 152014 Hom.: 5917 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.264 AC: 40238 AN: 152132 Hom.: 5919 Cov.: 32 AF XY: 0.258 AC XY: 19220 AN XY: 74366

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.273

Alfa AF: 0.332 Hom.: 14829

Bravo AF: 0.256

Asia WGS AF: 0.227 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.73

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: rs4660531; hg19: chr1-41839822;