rs6103560

Variant names:

• chr20-44009025-T-C
• rs6103560
• NM_001098797.2:c.411+2233T>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+2233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,050 control chromosomes in the GnomAD database, including 44,990 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 0.76 (44990 hom., cov: 31)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.411+2233T>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+2233T>C		intron_variant	Intron 3 of 8	2	NM_001098797.2	ENSP00000344724.3
TOX2	ENST00000372999.5	c.285+2233T>C		intron_variant	Intron 4 of 9	1		ENSP00000362090.1
TOX2	ENST00000358131.5	c.438+2233T>C		intron_variant	Intron 3 of 7	2		ENSP00000350849.5
TOX2	ENST00000423191.6	c.285+2233T>C		intron_variant	Intron 3 of 8	2		ENSP00000390278.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115516 AN: 151932 Hom.: 44935 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.760 AC: 115623 AN: 152050 Hom.: 44990 Cov.: 31 AF XY: 0.752 AC XY: 55878 AN XY: 74286

African (AFR) AF: 0.934 AC: 38780 AN: 41534

American (AMR) AF: 0.607 AC: 9272 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2645 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3403 AN: 5132

South Asian (SAS) AF: 0.725 AC: 3493 AN: 4820

European-Finnish (FIN) AF: 0.649 AC: 6850 AN: 10548

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48712 AN: 67958

Other (OTH) AF: 0.758 AC: 1600 AN: 2112

Alfa AF: 0.739 Hom.: 4676

Bravo AF: 0.764

Asia WGS AF: 0.680 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.43
PhyloP100		-1.0
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: rs6103560; hg19: chr20-42637665;