chr20-43945182-C-A

Variant names:

• chr20-43945182-C-A
• rs6031252
• NM_001098797.2:c.100-28185C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.100-28185C>A		intron_variant	Intron 1 of 8	ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9	c.100-28185C>A		intron_variant	Intron 1 of 8	2	NM_001098797.2	ENSP00000344724.3
TOX2	ENST00000372999.5	c.-152-9966C>A		intron_variant	Intron 1 of 9	1		ENSP00000362090.1
TOX2	ENST00000423191.6	c.-27-28185C>A		intron_variant	Intron 1 of 8	2		ENSP00000390278.1

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

African (AFR) AF: 0.408 AC: 16921 AN: 41434

American (AMR) AF: 0.0735 AC: 1125 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5184

South Asian (SAS) AF: 0.120 AC: 580 AN: 4826

European-Finnish (FIN) AF: 0.00472 AC: 50 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1172 AN: 68004

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.0614 Hom.: 3623

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
PhyloP100		0.29
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: rs6031252; hg19: chr20-42573822;