rs1111481

Positions:

• chr16-52498443-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080430.4(TOX3):​c.88-29869G>A variant causes a intron change. The variant allele was found at a frequency of 0.526 in 152,012 control chromosomes in the GnomAD database, including 21,566 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 0.53 (21566 hom., cov: 32)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

Genes affected

TOX3 (HGNC:11972): (TOX high mobility group box family member 3) The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-29869G>A		intron_variant		ENST00000219746.14	NP_001073899.2
TOX3	NM_001146188.2	c.75+20963G>A		intron_variant			NP_001139660.1
TOX3	XM_005255892.4	c.88-29869G>A		intron_variant			XP_005255949.1
TOX3	XM_047433909.1	c.75+20963G>A		intron_variant			XP_047289865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-29869G>A		intron_variant		2	NM_001080430.4	ENSP00000219746	A2
TOX3	ENST00000407228.7	c.75+20963G>A		intron_variant		2		ENSP00000385705	P2
TOX3	ENST00000563091.1	c.-21-29869G>A		intron_variant		4		ENSP00000457401
TOX3	ENST00000568436.1	c.88-22803G>A		intron_variant, NMD_transcript_variant		3		ENSP00000463843

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79858 AN: 151894 Hom.: 21544 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.526 AC: 79919 AN: 152012 Hom.: 21566 Cov.: 32 AF XY: 0.526 AC XY: 39051 AN XY: 74302

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.521

Alfa AF: 0.486 Hom.: 30047

Bravo AF: 0.532

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Benign	0.86

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: rs1111481; hg19: chr16-52532355;