8-59069973-C-G

Variant names:

• chr8-59069973-C-G
• rs380620
• NM_014729.3:c.102+48913G>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.102+48913G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,006 control chromosomes in the GnomAD database, including 23,073 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 0.54 (23073 hom., cov: 32)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX	NM_014729.3	c.102+48913G>C		intron_variant	Intron 1 of 8	ENST00000361421.2	NP_055544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX	ENST00000361421.2	c.102+48913G>C		intron_variant	Intron 1 of 8	1	NM_014729.3	ENSP00000354842.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82798 AN: 151888 Hom.: 23071 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.545 AC: 82843 AN: 152006 Hom.: 23073 Cov.: 32 AF XY: 0.548 AC XY: 40706 AN XY: 74312

African (AFR) AF: 0.440 AC: 18227 AN: 41406

American (AMR) AF: 0.522 AC: 7978 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2281 AN: 3468

East Asian (EAS) AF: 0.651 AC: 3370 AN: 5178

South Asian (SAS) AF: 0.731 AC: 3522 AN: 4820

European-Finnish (FIN) AF: 0.534 AC: 5643 AN: 10558

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40105 AN: 67974

Other (OTH) AF: 0.545 AC: 1151 AN: 2112

Alfa AF: 0.434 Hom.: 1229

Bravo AF: 0.535

Asia WGS AF: 0.596 AC: 2074 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.46
PhyloP100		0.56
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: rs380620; hg19: chr8-59982532;