chr20-44025707-T-C

Variant names:

• chr20-44025707-T-C
• rs6031301
• NM_001098797.2:c.411+18915T>C

Variant summary

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

The NM_001098797.2(TOX2):​c.411+18915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 150,738 control chromosomes in the GnomAD database, including 39,591 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 0.72 (39591 hom., cov: 25)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.411+18915T>C		intron_variant	Intron 3 of 8	ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9	c.411+18915T>C		intron_variant	Intron 3 of 8	2	NM_001098797.2	ENSP00000344724.3
TOX2	ENST00000372999.5	c.285+18915T>C		intron_variant	Intron 4 of 9	1		ENSP00000362090.1
TOX2	ENST00000358131.5	c.438+18915T>C		intron_variant	Intron 3 of 7	2		ENSP00000350849.5
TOX2	ENST00000423191.6	c.285+18915T>C		intron_variant	Intron 3 of 8	2		ENSP00000390278.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 108947 AN: 150622 Hom.: 39568 Cov.: 25

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.723 AC: 109016 AN: 150738 Hom.: 39591 Cov.: 25 AF XY: 0.722 AC XY: 53097 AN XY: 73508

African (AFR) AF: 0.746 AC: 30588 AN: 40996

American (AMR) AF: 0.695 AC: 10543 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2700 AN: 3464

East Asian (EAS) AF: 0.777 AC: 3873 AN: 4982

South Asian (SAS) AF: 0.633 AC: 2990 AN: 4726

European-Finnish (FIN) AF: 0.717 AC: 7476 AN: 10432

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.715 AC: 48401 AN: 67678

Other (OTH) AF: 0.721 AC: 1504 AN: 2086

Alfa AF: 0.718 Hom.: 10258

Bravo AF: 0.726

Asia WGS AF: 0.693 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		0.22
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: rs6031301; hg19: chr20-42654347;