rs7118395

Variant names:

• chr11-16177519-G-A
• rs7118395
• NM_001367873.1:c.777+6367C>T

Variant summary

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

The NM_001367873.1(SOX6):​c.777+6367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,636 control chromosomes in the GnomAD database, including 27,206 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 0.59 (27206 hom., cov: 31)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.777+6367C>T		intron_variant	Intron 6 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.777+6367C>T		intron_variant	Intron 6 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89055 AN: 151516 Hom.: 27171 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.588 AC: 89146 AN: 151636 Hom.: 27206 Cov.: 31 AF XY: 0.591 AC XY: 43822 AN XY: 74118

African (AFR) AF: 0.751 AC: 31086 AN: 41398

American (AMR) AF: 0.517 AC: 7851 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2382 AN: 3464

East Asian (EAS) AF: 0.754 AC: 3877 AN: 5140

South Asian (SAS) AF: 0.664 AC: 3194 AN: 4812

European-Finnish (FIN) AF: 0.538 AC: 5673 AN: 10544

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.490 AC: 33201 AN: 67772

Other (OTH) AF: 0.599 AC: 1261 AN: 2106

Alfa AF: 0.550 Hom.: 4128

Bravo AF: 0.596

Asia WGS AF: 0.741 AC: 2570 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.47
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7118395; hg19: chr11-16199065;