rs11047279

Variant names:

• chr12-24140368-C-T
• rs11047279
• NM_152989.5:c.-2+136848G>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+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
• Publications: 1 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 Gene-Disease associations (from GenCC):

• Lamb-Shaffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• developmental and speech delay due to SOX5 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-2+136848G>A		intron_variant	Intron 4 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-2+72975G>A		intron_variant	Intron 5 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-2+136848G>A		intron_variant	Intron 4 of 17		XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-2+72975G>A		intron_variant	Intron 5 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-2+136848G>A		intron_variant	Intron 4 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-2+72975G>A		intron_variant	Intron 3 of 4	5		ENSP00000496161.1

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

African (AFR) AF: 0.315 AC: 13038 AN: 41374

American (AMR) AF: 0.269 AC: 4107 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3466

East Asian (EAS) AF: 0.160 AC: 828 AN: 5168

South Asian (SAS) AF: 0.202 AC: 971 AN: 4806

European-Finnish (FIN) AF: 0.138 AC: 1452 AN: 10542

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15462 AN: 67908

Other (OTH) AF: 0.254 AC: 534 AN: 2106

Alfa AF: 0.235 Hom.: 6579

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
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs11047279; hg19: chr12-24293302;