Variant 3-181712330-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_003106.4(SOX2):c.-31C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,341,842 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 21 hom. )

Consequence

SOX2
NM_003106.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.417

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:):

SOX2-OT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 3-181712330-C-T is Benign according to our data. Variant chr3-181712330-C-T is described in ClinVar as [Benign]. Clinvar id is 378636.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00454 (689/151672) while in subpopulation NFE AF= 0.00535 (363/67790). AF 95% confidence interval is 0.0049. There are 2 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 689 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX2	NM_003106.4 linkuse as main transcript	c.-31C>T		5_prime_UTR_variant	1/1	ENST00000325404.3	NP_003097.1	P48431A0A0U3FYV6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2	ENST00000325404 linkuse as main transcript	c.-31C>T		5_prime_UTR_variant	1/1		NM_003106.4	ENSP00000323588.1		P48431

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

680

AN:

151562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00407

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00363

AC:

AN:

8268

Hom.:

AF XY:

0.00361

AC XY:

AN XY:

4432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00704

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00769

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00678

Gnomad OTH exome

AF:

0.00758

GnomAD4 exome

AF:

0.00470

AC:

5592

AN:

1190170

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

2677

AN XY:

573066

show subpopulations

Gnomad4 AFR exome

AF:

0.00361

Gnomad4 AMR exome

AF:

0.00393

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0000361

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.00204

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00454

AC:

689

AN:

151672

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

300

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.00408

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00152

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00437

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

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