Genetic Variant ENST00000466034.7:n.349+8883G>A (chr3-181708766-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000466034.7(SOX2-OT):n.349+8883G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,042 control chromosomes in the GnomAD database, including 3,984 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 0.20 ( 3984 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOX2-OT
ENST00000466034.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.342

Publications

7 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:

ENSG00000289435 (HGNC:):

ENSG00000289435 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 = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
SOX2-OT	NR_004053.3 link	n.768-6419G>A	intron_variant	Intron 3 of 4
SOX2-OT	NR_075089.1 link	n.767+8883G>A	intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1 link	n.482-30803G>A	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SOX2-OT	ENST00000466034.7 link	n.349+8883G>A	intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6 link	n.482-30803G>A	intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6 link	n.593+8883G>A	intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29619

AN:

151924

Hom.:

3969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0515

Gnomad FIN

AF:

0.0930

Gnomad MID

AF:

0.150

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.174

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.195

AC:

29673

AN:

152042

Hom.:

3984

Cov.:

AF XY:

0.187

AC XY:

13909

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.373

AC:

15438

AN:

41410

American (AMR)

AF:

0.127

AC:

1938

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

710

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0518

AC:

250

AN:

4830

European-Finnish (FIN)

AF:

0.0930

AC:

984

AN:

10580

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.144

AC:

9799

AN:

67978

Other (OTH)

AF:

0.171

AC:

362

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1129

2259

3388

4518

5647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.160

Hom.:

2895

Bravo

AF:

0.205

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

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

0.70

PhyloP100

0.34

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over