chr17-18668053-A-G

Position:

• chr17-18668053-A-G

Variant summary

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

The NM_001368135.1(FOXO3B):​c.*4256T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,132 control chromosomes in the GnomAD database, including 22,288 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 0.54 (22275 hom., cov: 31)
  • Exomes 𝑓: 0.54 (13 hom.)
• Consequence: FOXO3B NM_001368135.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

Genes affected

FOXO3B (HGNC:3822): (forkhead box O3B) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ZNF286B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3B	NM_001368135.1	c.*4256T>C		3_prime_UTR_variant	4/4	ENST00000395675.7	NP_001355064.1
FOXO3B	NM_001368134.1	c.*4256T>C		3_prime_UTR_variant	4/4		NP_001355063.1
ZNF286B	NR_160540.1	n.433-4826T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3B	ENST00000395675	c.*4256T>C		3_prime_UTR_variant	4/4		NM_001368135.1	ENSP00000499455.1
ZNF286B	ENST00000285274.9	n.347-4826T>C		intron_variant		3
ZNF286B	ENST00000668878.2	n.322-4826T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81893 AN: 151930 Hom.: 22228 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.536 AC: 45 AN: 84 Hom.: 13 Cov.: 0 AF XY: 0.583 AC XY: 35 AN XY: 60

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.539 AC: 82003 AN: 152048 Hom.: 22275 Cov.: 31 AF XY: 0.537 AC XY: 39900 AN XY: 74320

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.548

Alfa AF: 0.529 Hom.: 24635

Bravo AF: 0.540

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.4
DANN	Benign	0.29

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: rs9889937; hg19: chr17-18571366; COSMIC: COSV53381531; COSMIC: COSV53381531;