rs8004664

Positions:

• chr14-89568628-G-A
• chr14-89568628-G-C

Variant summary

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

The ENST00000345097.8(FOXN3):​c.-15+50400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,042 control chromosomes in the GnomAD database, including 17,614 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 0.44 (17614 hom., cov: 32)
• Consequence: FOXN3 ENST00000345097.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

Genes affected

FOXN3 (HGNC:1928): (forkhead box N3) This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN3	NM_001085471.2	c.-15+50400C>T		intron_variant			NP_001078940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN3	ENST00000345097.8	c.-15+50400C>T		intron_variant		1		ENSP00000343288	P4
FOXN3	ENST00000555353.5	c.-15+50400C>T		intron_variant		1		ENSP00000452227	A1
FOXN3	ENST00000555855.5	c.-118+50400C>T		intron_variant		5		ENSP00000451135

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67285 AN: 151924 Hom.: 17616 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.443 AC: 67283 AN: 152042 Hom.: 17614 Cov.: 32 AF XY: 0.439 AC XY: 32605 AN XY: 74290

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.469

Alfa AF: 0.505 Hom.: 2609

Bravo AF: 0.411

Asia WGS AF: 0.275 AC: 958 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	3.0
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8004664; hg19: chr14-90034972;