chr1-41365689-G-C

Variant names:

• chr1-41365689-G-C
• rs7547654
• ENST00000641094.2:c.414+3345G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641094.2(FOXO6):​c.414+3345G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,086 control chromosomes in the GnomAD database, including 14,032 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 0.40 (14032 hom., cov: 33)
• Consequence: FOXO6 ENST00000641094.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO6	NM_001291281.3	c.414+3345G>C		intron_variant	Intron 1 of 2		NP_001278210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO6	ENST00000641094.2	c.414+3345G>C		intron_variant	Intron 1 of 2			ENSP00000493184.1
FOXO6	ENST00000372591.1	n.423+3345G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61552 AN: 151968 Hom.: 14034 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.405 AC: 61557 AN: 152086 Hom.: 14032 Cov.: 33 AF XY: 0.413 AC XY: 30676 AN XY: 74332

African (AFR) AF: 0.204 AC: 8479 AN: 41508

American (AMR) AF: 0.524 AC: 8012 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3528 AN: 5172

South Asian (SAS) AF: 0.540 AC: 2603 AN: 4824

European-Finnish (FIN) AF: 0.540 AC: 5720 AN: 10586

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30689 AN: 67922

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.415 Hom.: 1724

Bravo AF: 0.392

Asia WGS AF: 0.577 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.38
PhyloP100		-2.7
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: rs7547654; hg19: chr1-41831361; COSMIC: COSV65428703;