rs1503452

chr11-16430585-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000396356.7(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 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367872.1	c.-4-89333G>A		intron_variant
SOX6	NM_033326.3	c.-5+45730G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000396356.7	c.-5+45730G>A		intron_variant		1		P4
SOX6	ENST00000529469.1	c.-5+3559G>A		intron_variant		4
SOX6	ENST00000530378.5	c.-5+45730G>A		intron_variant, NMD_transcript_variant		2
SOX6	ENST00000533658.5	n.333+35116G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.303

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.4
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1503452; hg19: chr11-16452132;