rs7979575

chr12-24125887-C-Gchr12-24125887-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+151329G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,072 control chromosomes in the GnomAD database, including 46,826 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 0.78 (46826 hom., cov: 31)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_001261414.3	c.-2+87456G>C		intron_variant
SOX5	NM_152989.5	c.-2+151329G>C		intron_variant
SOX5	XM_011520835.3	c.-2+151329G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000446891.7	c.-2+87456G>C		intron_variant		5
SOX5	ENST00000536729.2	c.-2+87456G>C		intron_variant		5
SOX5	ENST00000646273.1	c.-2+87456G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118824 AN: 151952 Hom.: 46769 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.782 AC: 118939 AN: 152072 Hom.: 46826 Cov.: 31 AF XY: 0.781 AC XY: 58101 AN XY: 74350

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.785

Alfa AF: 0.809 Hom.: 24076

Bravo AF: 0.779

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.071
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7979575; hg19: chr12-24278821;