chr14-89125050-T-C

Variant names:

• chr14-89125050-T-C
• rs4904509
• XR_007064299.1:n.638A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557572.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	ENST00000557572.1	TSL:3	c.*94A>G		3_prime_UTR	Exon 3 of 3	ENSP00000450783.1

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

African (AFR) AF: 0.864 AC: 6471 AN: 7490

American (AMR) AF: 0.659 AC: 14922 AN: 22638

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 6070 AN: 9216

East Asian (EAS) AF: 0.778 AC: 7031 AN: 9032

South Asian (SAS) AF: 0.694 AC: 38138 AN: 54966

European-Finnish (FIN) AF: 0.538 AC: 6310 AN: 11720

Middle Eastern (MID) AF: 0.708 AC: 837 AN: 1182

European-Non Finnish (NFE) AF: 0.639 AC: 94515 AN: 147930

Other (OTH) AF: 0.676 AC: 8776 AN: 12978

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

African (AFR) AF: 0.862 AC: 35812 AN: 41538

American (AMR) AF: 0.700 AC: 10714 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3468

East Asian (EAS) AF: 0.781 AC: 4047 AN: 5182

South Asian (SAS) AF: 0.716 AC: 3454 AN: 4824

European-Finnish (FIN) AF: 0.522 AC: 5521 AN: 10574

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43432 AN: 67996

Other (OTH) AF: 0.700 AC: 1476 AN: 2108

Alfa AF: 0.670 Hom.: 105289

Bravo AF: 0.726

Asia WGS AF: 0.757 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.72
DANN	Benign	0.42
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs4904509; hg19: chr14-89591394;