rs6584784

Variant names:

• chr10-107025357-G-A
• rs6584784
• NM_052918.5:c.559-68777C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-107025357-G-A
• chr10-107025357-G-C
• chr10-107025357-G-T

Variant summary

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

The NM_052918.5(SORCS1):​c.559-68777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,920 control chromosomes in the GnomAD database, including 11,636 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 0.39 (11636 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.559-68777C>T		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.559-68777C>T		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.559-68777C>T		intron	N/A	NP_001013049.1	Q8WY21-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.559-68777C>T		intron	N/A	ENSP00000263054.5	Q8WY21-1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58562 AN: 151802 Hom.: 11629 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.386 AC: 58618 AN: 151920 Hom.: 11636 Cov.: 32 AF XY: 0.386 AC XY: 28663 AN XY: 74246

African (AFR) AF: 0.476 AC: 19714 AN: 41430

American (AMR) AF: 0.426 AC: 6498 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1570 AN: 5152

South Asian (SAS) AF: 0.329 AC: 1583 AN: 4810

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23079 AN: 67940

Other (OTH) AF: 0.381 AC: 803 AN: 2110

Alfa AF: 0.349 Hom.: 40453

Bravo AF: 0.400

Asia WGS AF: 0.318 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.70
PhyloP100		0.0050
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: rs6584784; hg19: chr10-108785115;