NM_052918.5:c.558+9282G>C

Variant names:

• chr10-107154687-C-G
• rs601883
• NM_052918.5:c.558+9282G>C

Variant summary

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

The NM_052918.5(SORCS1):​c.558+9282G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,040 control chromosomes in the GnomAD database, including 2,614 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 0.18 (2614 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 6 publications found

Genes affected

SORCS1 (HGNC:16697): (sortilin related VPS10 domain containing receptor 1) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SORCS1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.558+9282G>C		intron_variant	Intron 1 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+9282G>C		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26901 AN: 151922 Hom.: 2607 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.177 AC: 26930 AN: 152040 Hom.: 2614 Cov.: 32 AF XY: 0.177 AC XY: 13145 AN XY: 74336

African (AFR) AF: 0.257 AC: 10654 AN: 41454

American (AMR) AF: 0.165 AC: 2520 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3464

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5160

South Asian (SAS) AF: 0.176 AC: 846 AN: 4810

European-Finnish (FIN) AF: 0.157 AC: 1659 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8971 AN: 67970

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.164 Hom.: 283

Bravo AF: 0.182

Asia WGS AF: 0.203 AC: 706 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs601883; hg19: chr10-108914445;