12-24236726-G-T

Variant names:

• chr12-24236726-G-T
• rs1464500
• NM_152989.5:c.-2+40490C>A

Variant summary

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

The NM_152989.5(SOX5):​c.-2+40490C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,138 control chromosomes in the GnomAD database, including 47,771 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 (47771 hom., cov: 33)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 13 publications found

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]

SOX5-AS1 (HGNC:53311): (SOX5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-2+40490C>A		intron_variant	Intron 4 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-76-23309C>A		intron_variant	Intron 4 of 16		NP_001248343.1
SOX5-AS1	NR_120472.1	n.446-1096G>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-76-23309C>A		intron_variant	Intron 4 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-2+40490C>A		intron_variant	Intron 4 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-76-23309C>A		intron_variant	Intron 2 of 4	5		ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119283 AN: 152020 Hom.: 47714 Cov.: 33

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.785 AC: 119397 AN: 152138 Hom.: 47771 Cov.: 33 AF XY: 0.787 AC XY: 58513 AN XY: 74378

African (AFR) AF: 0.928 AC: 38509 AN: 41518

American (AMR) AF: 0.752 AC: 11484 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2549 AN: 3466

East Asian (EAS) AF: 0.967 AC: 5014 AN: 5186

South Asian (SAS) AF: 0.725 AC: 3495 AN: 4820

European-Finnish (FIN) AF: 0.780 AC: 8254 AN: 10580

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47517 AN: 67970

Other (OTH) AF: 0.786 AC: 1663 AN: 2116

Alfa AF: 0.726 Hom.: 158610

Bravo AF: 0.793

Asia WGS AF: 0.850 AC: 2950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.23
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs1464500; hg19: chr12-24389660;