rs1040546

Variant names:

• chr20-44039748-G-A
• rs1040546
• NM_001098797.2:c.412-11558G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098797.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX2	NM_001098797.2	MANE Select	c.412-11558G>A		intron	N/A	NP_001092267.1
	TOX2	NM_001098798.2		c.439-11558G>A		intron	N/A	NP_001092268.1
	TOX2	NM_001098796.2		c.286-11558G>A		intron	N/A	NP_001092266.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX2	ENST00000341197.9	TSL:2 MANE Select	c.412-11558G>A		intron	N/A	ENSP00000344724.3
	TOX2	ENST00000372999.5	TSL:1	c.286-11558G>A		intron	N/A	ENSP00000362090.1
	TOX2	ENST00000358131.5	TSL:2	c.439-11558G>A		intron	N/A	ENSP00000350849.5

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

African (AFR) AF: 0.879 AC: 36512 AN: 41536

American (AMR) AF: 0.732 AC: 11197 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2888 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4104 AN: 5146

South Asian (SAS) AF: 0.695 AC: 3355 AN: 4824

European-Finnish (FIN) AF: 0.760 AC: 8036 AN: 10580

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51574 AN: 67974

Other (OTH) AF: 0.787 AC: 1660 AN: 2110

Alfa AF: 0.774 Hom.: 115370

Bravo AF: 0.795

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		-0.20
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: rs1040546; hg19: chr20-42668388;