rs12545204

Positions:

• chr8-58973753-T-A
• chr8-58973753-T-C
• chr8-58973753-T-G

Variant summary

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

The ENST00000361421.2(TOX):​c.103-13745A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,066 control chromosomes in the GnomAD database, including 40,581 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 (40581 hom., cov: 31)
• Consequence: TOX ENST00000361421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX	NM_014729.3	c.103-13745A>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.103-13745A>T		intron_variant		1	NM_014729.3	ENSP00000354842	P1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110122 AN: 151948 Hom.: 40561 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.725 AC: 110190 AN: 152066 Hom.: 40581 Cov.: 31 AF XY: 0.728 AC XY: 54093 AN XY: 74334

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.717

Alfa AF: 0.745 Hom.: 5039

Bravo AF: 0.702

Asia WGS AF: 0.760 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.84

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: rs12545204; hg19: chr8-59886312;