rs746867

chr8-59020822-T-C

Variant summary

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

The NM_014729.3(TOX):c.103-60814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,116 control chromosomes in the GnomAD database, including 3,686 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 0.21 (3686 hom., cov: 31)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX	NM_014729.3	c.103-60814A>G		intron_variant		ENST00000361421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX	ENST00000361421.2	c.103-60814A>G		intron_variant		1	NM_014729.3	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32519 AN: 151998 Hom.: 3689 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.214 AC: 32528 AN: 152116 Hom.: 3686 Cov.: 31 AF XY: 0.215 AC XY: 16003 AN XY: 74390

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.207

Alfa AF: 0.181 Hom.: 3081

Bravo AF: 0.222

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.7
Dann	Benign	0.86

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: rs746867; hg19: chr8-59933381;