rs6031252

Positions:

• chr20-43945182-C-A

Variant summary

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

The NM_001098797.2(TOX2):​c.100-28185C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,130 control chromosomes in the GnomAD database, including 3,826 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 0.14 (3826 hom., cov: 33)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

Genes affected

TOX2 (HGNC:16095): (TOX high mobility group box family member 2) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.100-28185C>A		intron_variant		ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9	c.100-28185C>A		intron_variant		2	NM_001098797.2	ENSP00000344724	P4
TOX2	ENST00000372999.5	c.-152-9966C>A		intron_variant		1		ENSP00000362090	A1
TOX2	ENST00000423191.6	c.-27-28185C>A		intron_variant		2		ENSP00000390278	A1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21471 AN: 152012 Hom.: 3803 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.142 AC: 21548 AN: 152130 Hom.: 3826 Cov.: 33 AF XY: 0.140 AC XY: 10382 AN XY: 74362

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0454 Hom.: 872

Bravo AF: 0.160

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.53

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: rs6031252; hg19: chr20-42573822;