chr16-52473537-G-A

Variant names:

• chr16-52473537-G-A
• rs4784217
• NM_001080430.4:c.88-4963C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOX3	NM_001080430.4	c.88-4963C>T		intron_variant	Intron 1 of 6	ENST00000219746.14	NP_001073899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOX3	ENST00000219746.14	c.88-4963C>T		intron_variant	Intron 1 of 6	2	NM_001080430.4	ENSP00000219746.9
TOX3	ENST00000407228.7	c.76-4963C>T		intron_variant	Intron 2 of 7	2		ENSP00000385705.3
TOX3	ENST00000563091.1	c.-21-4963C>T		intron_variant	Intron 1 of 3	4		ENSP00000457401.1
TOX3	ENST00000568436.1	n.*14+1994C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.484 AC: 20062 AN: 41420

American (AMR) AF: 0.545 AC: 8320 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1956 AN: 3458

East Asian (EAS) AF: 0.776 AC: 4003 AN: 5160

South Asian (SAS) AF: 0.676 AC: 3263 AN: 4824

European-Finnish (FIN) AF: 0.423 AC: 4462 AN: 10558

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37183 AN: 68008

Other (OTH) AF: 0.554 AC: 1173 AN: 2116

Alfa AF: 0.507 Hom.: 2587

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
PhyloP100		0.093
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4784217; hg19: chr16-52507449;