8-58822280-C-G

Position:

• chr8-58822280-C-G

Variant summary

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

The NM_014729.3(TOX):​c.1005+4542G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,140 control chromosomes in the GnomAD database, including 6,813 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 0.24 (6813 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOX	NM_014729.3	c.1005+4542G>C		intron_variant		ENST00000361421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOX	ENST00000361421.2	c.1005+4542G>C		intron_variant		1	NM_014729.3	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36504 AN: 152024 Hom.: 6797 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.240 AC: 36557 AN: 152140 Hom.: 6813 Cov.: 32 AF XY: 0.237 AC XY: 17665 AN XY: 74390

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.218

Alfa AF: 0.0683 Hom.: 75

Bravo AF: 0.254

Asia WGS AF: 0.138 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.72

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: rs7817609; hg19: chr8-59734839;