rs4784217

Positions:

• chr16-52473537-G-A
• chr16-52473537-G-C

Variant summary

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

The NM_001080430.4(TOX3):​c.88-4963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,026 control chromosomes in the GnomAD database, including 22,084 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 (22084 hom., cov: 33)
• Consequence: TOX3 NM_001080430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-4963C>T		intron_variant		ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-4963C>T		intron_variant		2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.76-4963C>T		intron_variant		2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-21-4963C>T		intron_variant		4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.*14+1994C>T		intron_variant		3		ENSP00000463843.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81216 AN: 151908 Hom.: 22066 Cov.: 33

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.535 AC: 81260 AN: 152026 Hom.: 22084 Cov.: 33 AF XY: 0.535 AC XY: 39748 AN XY: 74310

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.554

Alfa AF: 0.508 Hom.: 2502

Bravo AF: 0.542

Asia WGS AF: 0.726 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4784217; hg19: chr16-52507449;