rs2028162

chr11-16225929-T-Cchr11-16225929-T-G

Variant summary

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

The NM_001367873.1(SOX6):c.535+8653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,108 control chromosomes in the GnomAD database, including 3,914 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 0.21 (3914 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1	c.535+8653A>G		intron_variant		ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1	c.535+8653A>G		intron_variant			NM_001367873.1	A2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31320 AN: 151990 Hom.: 3911 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.206 AC: 31325 AN: 152108 Hom.: 3914 Cov.: 32 AF XY: 0.206 AC XY: 15329 AN XY: 74348

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.204

Alfa AF: 0.250 Hom.: 2553

Bravo AF: 0.208

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	13
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs2028162; hg19: chr11-16247475;