8-58849175-T-C

Variant names:

• chr8-58849175-T-C
• rs1349115
• NM_014729.3:c.693+2349A>G

Variant summary

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

The NM_014729.3(TOX):​c.693+2349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,962 control chromosomes in the GnomAD database, including 7,198 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 0.30 (7198 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.693+2349A>G		intron_variant	Intron 4 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.693+2349A>G		intron_variant	Intron 4 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45919 AN: 151846 Hom.: 7190 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0806

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.302 AC: 45948 AN: 151962 Hom.: 7198 Cov.: 32 AF XY: 0.300 AC XY: 22295 AN XY: 74286

African (AFR) AF: 0.259 AC: 10755 AN: 41484

American (AMR) AF: 0.313 AC: 4781 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.0808 AC: 418 AN: 5172

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2869 AN: 10540

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23490 AN: 67900

Other (OTH) AF: 0.335 AC: 707 AN: 2108

Alfa AF: 0.344 Hom.: 13894

Bravo AF: 0.303

Asia WGS AF: 0.230 AC: 797 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.62
DANN	Benign	0.79
PhyloP100		-0.95
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: rs1349115; hg19: chr8-59761734;