3-181739813-T-C

Variant names:

• chr3-181739813-T-C
• rs6765739
• ENST00000466034.7:n.762T>C

Variant summary

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

The ENST00000466034.7(SOX2-OT):​n.762T>C 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 0.329 in 152,060 control chromosomes in the GnomAD database, including 8,698 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 0.33 (8698 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SOX2-OT ENST00000466034.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.1120T>C		non_coding_transcript_exon_variant	Exon 5 of 5
SOX2-OT	NR_075089.1	n.1012T>C		non_coding_transcript_exon_variant	Exon 4 of 4
SOX2-OT	NR_075090.1	n.726T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000466034.7	n.762T>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
SOX2-OT	ENST00000476964.6	n.726T>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
SOX2-OT	ENST00000491282.6	n.838T>C		non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49981 AN: 151934 Hom.: 8692 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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: 4

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.329 AC: 50001 AN: 152052 Hom.: 8698 Cov.: 32 AF XY: 0.326 AC XY: 24243 AN XY: 74304

African (AFR) AF: 0.209 AC: 8696 AN: 41514

American (AMR) AF: 0.358 AC: 5466 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1735 AN: 5144

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4816

European-Finnish (FIN) AF: 0.371 AC: 3915 AN: 10552

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26773 AN: 67974

Other (OTH) AF: 0.330 AC: 695 AN: 2108

Alfa AF: 0.370 Hom.: 21363

Bravo AF: 0.327

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.7
DANN	Benign	0.66
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs6765739; hg19: chr3-181457601;