8-59100042-T-C

Variant names:

• chr8-59100042-T-C
• rs2561145
• NM_014729.3:c.102+18844A>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.102+18844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,580 control chromosomes in the GnomAD database, including 19,070 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 0.46 (19070 hom., cov: 31)
• Consequence: TOX NM_014729.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	NM_014729.3	MANE Select	c.102+18844A>G		intron	N/A	NP_055544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX	ENST00000361421.2	TSL:1 MANE Select	c.102+18844A>G		intron	N/A	ENSP00000354842.1
	TOX	ENST00000890858.1		c.102+18844A>G		intron	N/A	ENSP00000560917.1
	TOX	ENST00000966264.1		c.102+18844A>G		intron	N/A	ENSP00000636323.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69396 AN: 151462 Hom.: 19065 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.458 AC: 69402 AN: 151580 Hom.: 19070 Cov.: 31 AF XY: 0.465 AC XY: 34409 AN XY: 74024

African (AFR) AF: 0.140 AC: 5794 AN: 41446

American (AMR) AF: 0.480 AC: 7314 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3468

East Asian (EAS) AF: 0.693 AC: 3564 AN: 5142

South Asian (SAS) AF: 0.749 AC: 3586 AN: 4786

European-Finnish (FIN) AF: 0.585 AC: 6065 AN: 10370

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.585 AC: 39715 AN: 67834

Other (OTH) AF: 0.465 AC: 980 AN: 2108

Alfa AF: 0.548 Hom.: 32867

Bravo AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.020
DANN	Benign	0.39
PhyloP100		-0.69
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: rs2561145; hg19: chr8-60012601;