Genetic Variant ENSG00000307532:n.121C>T (chr16-52547512-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000826906.1(ENSG00000307532):n.121C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,102 control chromosomes in the GnomAD database, including 10,252 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 0.35 ( 10213 hom., cov: 29)

Exomes 𝑓: 0.30 ( 39 hom. )

Consequence

ENSG00000307532
ENST00000826906.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

8 publications found

Variant links:

Genes affected

ENSG00000307532 (HGNC:):

ENSG00000307532 links:

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]

TOX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOX3	NM_001146188.2 link	c.-100+202G>A		intron_variant	Intron 1 of 7		NP_001139660.1	O15405-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000307532	ENST00000826906.1 link	n.121C>T	non_coding_transcript_exon_variant	Exon 1 of 4
ENSG00000307532	ENST00000826907.1 link	n.214C>T	non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000307532	ENST00000826908.1 link	n.213C>T	non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53324

AN:

151236

Hom.:

10180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.348

GnomAD4 exome

AF:

0.303

AC:

226

AN:

746

Hom.:

Cov.:

AF XY:

0.319

AC XY:

159

AN XY:

498

show subpopulations

African (AFR)

AF:

0.350

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.563

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AF:

0.289

AC:

AN:

142

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.289

AC:

140

AN:

484

Other (OTH)

AF:

0.397

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53421

AN:

151356

Hom.:

10213

Cov.:

AF XY:

0.355

AC XY:

26280

AN XY:

73934

show subpopulations

African (AFR)

AF:

0.469

AC:

19346

AN:

41226

American (AMR)

AF:

0.379

AC:

5762

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1348

AN:

3470

East Asian (EAS)

AF:

0.620

AC:

3118

AN:

5032

South Asian (SAS)

AF:

0.264

AC:

1262

AN:

4772

European-Finnish (FIN)

AF:

0.317

AC:

3333

AN:

10518

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18118

AN:

67814

Other (OTH)

AF:

0.353

AC:

743

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1593

3185

4778

6370

7963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.279

Hom.:

4001

Bravo

AF:

0.368

Asia WGS

AF:

0.431

AC:

1498

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

(source)

DANN

Benign

0.87

PhyloP100

0.24

PromoterAI

0.028

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over