rs2014408

Variant names:

• chr11-16343736-C-T
• rs2014408
• NM_001367873.1:c.-4-2484G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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):

• Tolchin-Le Caignec syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367873.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001367873.1	MANE Select	c.-4-2484G>A		intron	N/A	NP_001354802.1
	SOX6	NM_001145819.2		c.-4-2484G>A		intron	N/A	NP_001139291.2
	SOX6	NM_033326.3		c.-4-2484G>A		intron	N/A	NP_201583.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.-4-2484G>A		intron	N/A	ENSP00000507545.1
	SOX6	ENST00000528429.5	TSL:1	c.-4-2484G>A		intron	N/A	ENSP00000433233.1
	SOX6	ENST00000396356.7	TSL:1	c.-4-2484G>A		intron	N/A	ENSP00000379644.3

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

African (AFR) AF: 0.0639 AC: 2653 AN: 41504

American (AMR) AF: 0.292 AC: 4444 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 629 AN: 3464

East Asian (EAS) AF: 0.239 AC: 1232 AN: 5154

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13906 AN: 67752

Other (OTH) AF: 0.175 AC: 369 AN: 2106

Alfa AF: 0.174 Hom.: 428

Bravo AF: 0.179

Asia WGS AF: 0.185 AC: 643 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.69
PhyloP100		1.4
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: rs2014408; hg19: chr11-16365282;