rs11915160

Positions:

• chr3-181713783-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003106.4(SOX2):​c.*469C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.114 in 284,722 control chromosomes in the GnomAD database, including 2,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1143 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1099 hom.)
• Consequence: SOX2 NM_003106.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.99

Genes affected

SOX2 (HGNC:11195): (SRY-box transcription factor 2) This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach. Mutations in this gene have been associated with optic nerve hypoplasia and with syndromic microphthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT). [provided by RefSeq, Jul 2008]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-181713783-C-A is Benign according to our data. Variant chr3-181713783-C-A is described in ClinVar as [Benign]. Clinvar id is 1226892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2	NM_003106.4	c.*469C>A		3_prime_UTR_variant	1/1	ENST00000325404.3
SOX2-OT	NR_075091.1	n.783-1402C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2	ENST00000325404.3	c.*469C>A		3_prime_UTR_variant	1/1		NM_003106.4	P1
SOX2-OT	ENST00000626948.3	n.837-1402C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16820 AN: 152088 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.118 AC: 15696 AN: 132516 Hom.: 1099 Cov.: 0 AF XY: 0.119 AC XY: 7504 AN XY: 62882

Gnomad4 AFR exome AF: 0.0368

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0664

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.110 AC: 16817 AN: 152206 Hom.: 1143 Cov.: 32 AF XY: 0.109 AC XY: 8088 AN XY: 74400

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.123

Alfa AF: 0.142 Hom.: 861

Bravo AF: 0.112

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11915160; hg19: chr3-181431571; COSMIC: COSV57621485; COSMIC: COSV57621485;