chr3-181713783-C-A

Variant names:

• chr3-181713783-C-A
• rs11915160
• NM_003106.4:c.*469C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.99
• Publications: 23 publications found

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]

ENSG00000294981 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 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 VariationId is 1226892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SOX2	NM_003106.4	c.*469C>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000325404.3	NP_003097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2	ENST00000325404.3	c.*469C>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_003106.4	ENSP00000323588.1

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

African (AFR) AF: 0.0368 AC: 166 AN: 4506

American (AMR) AF: 0.127 AC: 768 AN: 6038

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 529 AN: 5786

East Asian (EAS) AF: 0.0147 AC: 201 AN: 13720

South Asian (SAS) AF: 0.0664 AC: 379 AN: 5704

European-Finnish (FIN) AF: 0.124 AC: 1960 AN: 15752

Middle Eastern (MID) AF: 0.0753 AC: 44 AN: 584

European-Non Finnish (NFE) AF: 0.146 AC: 10482 AN: 71630

Other (OTH) AF: 0.133 AC: 1167 AN: 8796

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

African (AFR) AF: 0.0387 AC: 1605 AN: 41526

American (AMR) AF: 0.137 AC: 2100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5184

South Asian (SAS) AF: 0.0727 AC: 351 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10623 AN: 68012

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.142 Hom.: 3286

Bravo AF: 0.112

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		4.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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