rs11024028

Positions:

• chr11-16735326-C-G

Variant summary

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

The NM_001367872.1(SOX6):​c.-261+3099G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,192 control chromosomes in the GnomAD database, including 1,619 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 0.13 (1619 hom., cov: 32)
• Consequence: SOX6 NM_001367872.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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]

C11orf58 (HGNC:16990): (chromosome 11 open reading frame 58)

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 = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX6	NM_001367872.1	c.-261+3099G>C		intron_variant			NP_001354801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000530378.5	c.-335+1013G>C		intron_variant, NMD_transcript_variant		2		ENSP00000432577
SOX6	ENST00000524520.5	n.353+1013G>C		intron_variant, non_coding_transcript_variant		5
SOX6	ENST00000525259.1	n.267+1013G>C		intron_variant, non_coding_transcript_variant		4
C11orf58	ENST00000527893.5	n.405-9275C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19454 AN: 152076 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.128 AC: 19445 AN: 152192 Hom.: 1619 Cov.: 32 AF XY: 0.123 AC XY: 9187 AN XY: 74394

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.153

Alfa AF: 0.162 Hom.: 277

Bravo AF: 0.124

Asia WGS AF: 0.0290 AC: 101 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	0.19
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11024028; hg19: chr11-16756873;