chr3-181708766-G-A

Variant names:

• chr3-181708766-G-A
• rs35788479
• ENST00000466034.7:n.349+8883G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 7 publications found

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]

ENSG00000289435 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466034.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	NR_004053.3		n.768-6419G>A		intron	N/A
	SOX2-OT	NR_075089.1		n.767+8883G>A		intron	N/A
	SOX2-OT	NR_075090.1		n.482-30803G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000466034.7	TSL:1	n.349+8883G>A		intron	N/A
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-30803G>A		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.593+8883G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29619 AN: 151924 Hom.: 3969 Cov.: 33

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: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.195 AC: 29673 AN: 152042 Hom.: 3984 Cov.: 33 AF XY: 0.187 AC XY: 13909 AN XY: 74356

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: 0 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: 47 AN: 292

European-Non Finnish (NFE) AF: 0.144 AC: 9799 AN: 67978

Other (OTH) AF: 0.171 AC: 362 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35788479; hg19: chr3-181426554;