rs826729

Positions:

• chr8-58826354-G-A
• chr8-58826354-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.1005+468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,112 control chromosomes in the GnomAD database, including 40,279 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 0.72 (40279 hom., cov: 33)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX	NM_014729.3	c.1005+468C>T		intron_variant		ENST00000361421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX	ENST00000361421.2	c.1005+468C>T		intron_variant		1	NM_014729.3	P1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109448 AN: 151994 Hom.: 40252 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.720 AC: 109524 AN: 152112 Hom.: 40279 Cov.: 33 AF XY: 0.727 AC XY: 54079 AN XY: 74356

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.749

Alfa AF: 0.725 Hom.: 4768

Bravo AF: 0.712

Asia WGS AF: 0.871 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.71

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: rs826729; hg19: chr8-59738913;