Genetic Variant ENST00000826906.1: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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