Genetic Variant SOX2-OT:n.482-40751T>G (chr3-181698818-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000476964.6(SOX2-OT):n.482-40751T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,436 control chromosomes in the GnomAD database, including 30,833 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 0.62 ( 30831 hom., cov: 29)

Exomes 𝑓: 0.38 ( 2 hom. )

Consequence

SOX2-OT
ENST00000476964.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617

Publications

6 publications found

Variant links:

Genes affected

SOX2-OT (HGNC:20209): (SOX2 overlapping transcript) This gene produces alternatively spliced long non-coding RNAs. These RNAs were observed to be upregulated in tumor cells and positively correlated to expression of the SRY-box 2 gene. Overexpression of these transcripts may promote cell proliferation. [provided by RefSeq, Dec 2017]

SOX2-OT links:

ENSG00000239381 (HGNC:):

ENSG00000239381 links:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
SOX2-OT	NR_004053.3 link	n.482-780T>G	intron_variant	Intron 2 of 4
SOX2-OT	NR_075089.1 link	n.482-780T>G	intron_variant	Intron 2 of 3
SOX2-OT	NR_075090.1 link	n.482-40751T>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SOX2-OT	ENST00000476964.6 link	n.482-40751T>G	intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6 link	n.308-780T>G	intron_variant	Intron 3 of 4	1
SOX2-OT	ENST00000498731.6 link	n.255-780T>G	intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93378

AN:

151294

Hom.:

30786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.561

GnomAD4 exome

AF:

0.385

AC:

AN:

Hom.:

Cov.:

AF XY:

0.278

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.350

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.617

AC:

93485

AN:

151410

Hom.:

30831

Cov.:

AF XY:

0.612

AC XY:

45271

AN XY:

73916

show subpopulations

African (AFR)

AF:

0.851

AC:

35206

AN:

41388

American (AMR)

AF:

0.579

AC:

8812

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1547

AN:

3448

East Asian (EAS)

AF:

0.757

AC:

3878

AN:

5126

South Asian (SAS)

AF:

0.268

AC:

1269

AN:

4742

European-Finnish (FIN)

AF:

0.549

AC:

5730

AN:

10442

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35228

AN:

67734

Other (OTH)

AF:

0.560

AC:

1178

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1626

3253

4879

6506

8132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.537

Hom.:

25405

Bravo

AF:

0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.62

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over