rs1503452

Variant names:

• chr11-16430585-C-T
• rs1503452
• ENST00000396356.7:c.-5+45730G>A

Variant summary

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

The NM_033326.3(SOX6):​c.-5+45730G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,038 control chromosomes in the GnomAD database, including 8,351 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 0.31 (8351 hom., cov: 32)
• Consequence: SOX6 NM_033326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 1 publications found

Genes affected

SOX6 (HGNC:16421): (SRY-box transcription factor 6) This gene encodes a member of the D subfamily of sex determining region y-related transcription factors that are characterized by a conserved DNA-binding domain termed the high mobility group box and by their ability to bind the minor groove of DNA. The encoded protein is a transcriptional activator that is required for normal development of the central nervous system, chondrogenesis and maintenance of cardiac and skeletal muscle cells. The encoded protein interacts with other family members to cooperatively activate gene expression. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

SOX6 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Tolchin-Le Caignec syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033326.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_033326.3		c.-5+45730G>A		intron	N/A	NP_201583.2	P35712-3
	SOX6	NM_001367872.1		c.-4-89333G>A		intron	N/A	NP_001354801.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000396356.7	TSL:1	c.-5+45730G>A		intron	N/A	ENSP00000379644.3	P35712-3
	SOX6	ENST00000887067.1		c.-5+45730G>A		intron	N/A	ENSP00000557126.1
	SOX6	ENST00000887062.1		c.-5+45730G>A		intron	N/A	ENSP00000557121.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47425 AN: 151916 Hom.: 8354 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47421 AN: 152038 Hom.: 8351 Cov.: 32 AF XY: 0.310 AC XY: 23060 AN XY: 74302

African (AFR) AF: 0.167 AC: 6920 AN: 41494

American (AMR) AF: 0.254 AC: 3879 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.113 AC: 585 AN: 5168

South Asian (SAS) AF: 0.294 AC: 1414 AN: 4812

European-Finnish (FIN) AF: 0.469 AC: 4956 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26898 AN: 67944

Other (OTH) AF: 0.303 AC: 641 AN: 2114

Alfa AF: 0.352 Hom.: 1620

Bravo AF: 0.289

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1503452; hg19: chr11-16452132;