3-181711518-A-T

Variant names:

• chr3-181711518-A-T
• rs35095647
• ENST00000466034.7:n.349+11635A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000466034.7(SOX2-OT):​n.349+11635A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 151,858 control chromosomes in the GnomAD database, including 4 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 0.0028 (4 hom., cov: 31)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.768-3667A>T		intron	N/A
	SOX2-OT	NR_075089.1		n.767+11635A>T		intron	N/A
	SOX2-OT	NR_075090.1		n.482-28051A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000466034.7	TSL:1	n.349+11635A>T		intron	N/A
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-28051A>T		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.593+11635A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00279 AC: 423 AN: 151742 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00355

Gnomad OTH AF: 0.00192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00278 AC: 422 AN: 151858 Hom.: 4 Cov.: 31 AF XY: 0.00334 AC XY: 248 AN XY: 74212

African (AFR) AF: 0.0000966 AC: 4 AN: 41404

American (AMR) AF: 0.000786 AC: 12 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.0152 AC: 161 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00355 AC: 241 AN: 67918

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.00625 Hom.: 4

Bravo AF: 0.00130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.1
DANN	Benign	0.84
PhyloP100		-0.19
PromoterAI		0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs35095647; hg19: chr3-181429306;