NM_052918.5:c.559-47676G>A

Variant names:

• chr10-107004256-C-T
• rs6584777
• NM_052918.5:c.559-47676G>A

Variant summary

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

The NM_052918.5(SORCS1):​c.559-47676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 150,368 control chromosomes in the GnomAD database, including 15,516 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 0.41 (15516 hom., cov: 29)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-47676G>A		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.559-47676G>A		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.412 AC: 61883 AN: 150262 Hom.: 15474 Cov.: 29

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.412 AC: 61982 AN: 150368 Hom.: 15516 Cov.: 29 AF XY: 0.407 AC XY: 29807 AN XY: 73296

African (AFR) AF: 0.714 AC: 29118 AN: 40776

American (AMR) AF: 0.288 AC: 4353 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3464

East Asian (EAS) AF: 0.159 AC: 817 AN: 5124

South Asian (SAS) AF: 0.282 AC: 1345 AN: 4766

European-Finnish (FIN) AF: 0.278 AC: 2795 AN: 10052

Middle Eastern (MID) AF: 0.428 AC: 124 AN: 290

European-Non Finnish (NFE) AF: 0.309 AC: 20960 AN: 67804

Other (OTH) AF: 0.380 AC: 796 AN: 2092

Alfa AF: 0.327 Hom.: 5598

Bravo AF: 0.429

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.6
DANN	Benign	0.25
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6584777; hg19: chr10-108764014;