Variant rs11915160 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.99

Variant links:

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 links:

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]

SOX2-OT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SOX2	NM_003106.4 linkuse as main transcript	c.*469C>A		3_prime_UTR_variant	1/1	ENST00000325404.3	NP_003097.1
SOX2-OT	NR_075091.1 linkuse as main transcript	n.783-1402C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2	ENST00000325404.3 linkuse as main transcript	c.*469C>A		3_prime_UTR_variant	1/1		NM_003106.4	ENSP00000323588	P1
SOX2-OT	ENST00000626948.3 linkuse as main transcript	n.837-1402C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16820

AN:

152088

Hom.:

1144

Cov.:

show subpopulations

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.:

AF XY:

0.119

AC XY:

7504

AN XY:

62882

show subpopulations

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.:

AF XY:

0.109

AC XY:

8088

AN XY:

74400

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over