rs4904509

Positions:

• chr14-89125050-T-C
• chr14-89125050-T-G

Variant summary

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

The XR_007064299.1(LOC124903357):​n.638A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 429,346 control chromosomes in the GnomAD database, including 100,190 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 0.71 (39024 hom., cov: 33)
  • Exomes 𝑓: 0.66 (61166 hom.)
• Consequence: LOC124903357 XR_007064299.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

LOC124903357 (HGNC:):

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903357	XR_007064299.1	n.638A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN3	ENST00000557572.1	c.*94A>G		3_prime_UTR_variant	3/3	3		ENSP00000450783

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107432 AN: 152076 Hom.: 38958 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.661 AC: 183070 AN: 277152 Hom.: 61166 Cov.: 0 AF XY: 0.663 AC XY: 104457 AN XY: 157580

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.659

Gnomad4 EAS exome AF: 0.778

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.707 AC: 107557 AN: 152194 Hom.: 39024 Cov.: 33 AF XY: 0.702 AC XY: 52217 AN XY: 74410

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.700

Alfa AF: 0.658 Hom.: 61604

Bravo AF: 0.726

Asia WGS AF: 0.757 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.72
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4904509; hg19: chr14-89591394;