8-58812489-A-G

Variant names:

• chr8-58812489-A-G
• rs2693430
• NM_014729.3:c.1392+2849T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014729.3(TOX):​c.1392+2849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,678 control chromosomes in the GnomAD database, including 10,411 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 0.35 (10411 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014729.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	NM_014729.3	MANE Select	c.1392+2849T>C		intron	N/A	NP_055544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	ENST00000361421.2	TSL:1 MANE Select	c.1392+2849T>C		intron	N/A	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53324 AN: 151560 Hom.: 10400 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.352 AC: 53369 AN: 151678 Hom.: 10411 Cov.: 32 AF XY: 0.353 AC XY: 26187 AN XY: 74112

African (AFR) AF: 0.534 AC: 22075 AN: 41366

American (AMR) AF: 0.294 AC: 4487 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 768 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2041 AN: 5138

South Asian (SAS) AF: 0.405 AC: 1938 AN: 4790

European-Finnish (FIN) AF: 0.321 AC: 3369 AN: 10504

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17737 AN: 67848

Other (OTH) AF: 0.327 AC: 691 AN: 2112

Alfa AF: 0.292 Hom.: 22661

Bravo AF: 0.356

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.65
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2693430; hg19: chr8-59725048;