rs1040546

Positions:

• chr20-44039748-G-A
• chr20-44039748-G-C
• chr20-44039748-G-T

Variant summary

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

The NM_001098797.2(TOX2):​c.412-11558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,142 control chromosomes in the GnomAD database, including 47,949 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 0.79 (47949 hom., cov: 31)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.412-11558G>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.412-11558G>A		intron_variant		2	NM_001098797.2	ENSP00000344724	P4

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120195 AN: 152024 Hom.: 47896 Cov.: 31

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.791 AC: 120305 AN: 152142 Hom.: 47949 Cov.: 31 AF XY: 0.789 AC XY: 58643 AN XY: 74348

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.787

Alfa AF: 0.769 Hom.: 66947

Bravo AF: 0.795

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.56

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: rs1040546; hg19: chr20-42668388;