rs11047279

chr12-24140368-C-T

Variant summary

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

The NM_152989.5(SOX5):c.-2+136848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,838 control chromosomes in the GnomAD database, including 4,834 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 0.25 (4834 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

Genes affected

SOX5 (HGNC:11201): (SRY-box transcription factor 5) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_001261414.3	c.-2+72975G>A		intron_variant
SOX5	NM_152989.5	c.-2+136848G>A		intron_variant
SOX5	XM_011520835.3	c.-2+136848G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000446891.7	c.-2+72975G>A		intron_variant		5
SOX5	ENST00000536729.2	c.-2+72975G>A		intron_variant		5
SOX5	ENST00000646273.1	c.-2+72975G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37349 AN: 151722 Hom.: 4813 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.246 AC: 37416 AN: 151838 Hom.: 4834 Cov.: 32 AF XY: 0.243 AC XY: 18009 AN XY: 74196

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.254

Alfa AF: 0.234 Hom.: 5443

Bravo AF: 0.258

Asia WGS AF: 0.221 AC: 769 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	0.53
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11047279; hg19: chr12-24293302;