rs4737532

Positions:

• chr8-59025084-G-A
• chr8-59025084-G-C

Variant summary

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

The NM_014729.3(TOX):​c.103-65076C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,960 control chromosomes in the GnomAD database, including 46,801 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 0.78 (46801 hom., cov: 30)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

Genes affected

TOX (HGNC:18988): (thymocyte selection associated high mobility group box) The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009]

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 (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-65076C>T		intron_variant		ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.103-65076C>T		intron_variant		1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118132 AN: 151842 Hom.: 46792 Cov.: 30

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.778 AC: 118185 AN: 151960 Hom.: 46801 Cov.: 30 AF XY: 0.771 AC XY: 57232 AN XY: 74270

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.759

Alfa AF: 0.831 Hom.: 106736

Bravo AF: 0.762

Asia WGS AF: 0.572 AC: 1993 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	0.74
DANN	Benign	0.56

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: rs4737532; hg19: chr8-59937643;