rs4756846

Positions:

• chr11-16381965-T-C

Variant summary

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

The ENST00000528429.5(SOX6):​c.-5+20835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 152,018 control chromosomes in the GnomAD database, including 656 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 0.087 (656 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX6	NM_001145811.2	c.-5+26733A>G		intron_variant			NP_001139283.1
SOX6	NM_001145819.2	c.-5+20835A>G		intron_variant			NP_001139291.2
SOX6	NM_001367872.1	c.-4-40713A>G		intron_variant			NP_001354801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000396356.7	c.-4-40713A>G		intron_variant		1		ENSP00000379644	P4
SOX6	ENST00000527619.6	c.-5+20694A>G		intron_variant		1		ENSP00000434455	A2
SOX6	ENST00000528429.5	c.-5+20835A>G		intron_variant		1		ENSP00000433233	A2

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13164 AN: 151900 Hom.: 655 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0935

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

GnomAD4 genome AF: 0.0867 AC: 13175 AN: 152018 Hom.: 656 Cov.: 32 AF XY: 0.0856 AC XY: 6363 AN XY: 74300

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0925

Alfa AF: 0.101 Hom.: 1068

Bravo AF: 0.0818

Asia WGS AF: 0.0150 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4756846; hg19: chr11-16403511;