rs2014408

chr11-16343736-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001367873.1(SOX6):c.-4-2484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,780 control chromosomes in the GnomAD database, including 2,732 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 0.17 (2732 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1	c.-4-2484G>A		intron_variant		ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1	c.-4-2484G>A		intron_variant			NM_001367873.1	A2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26057 AN: 151662 Hom.: 2727 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.172 AC: 26070 AN: 151780 Hom.: 2732 Cov.: 32 AF XY: 0.172 AC XY: 12787 AN XY: 74172

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.175

Alfa AF: 0.177 Hom.: 424

Bravo AF: 0.179

Asia WGS AF: 0.185 AC: 643 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	18
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2014408; hg19: chr11-16365282;