rs17277986

Variant names:

• chr10-106998968-C-T
• rs17277986
• NM_052918.5:c.559-42388G>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.559-42388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,074 control chromosomes in the GnomAD database, including 4,377 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 0.22 (4377 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 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.559-42388G>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.559-42388G>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.559-42388G>A		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.559-42388G>A		intron	N/A	ENSP00000263054.5	Q8WY21-1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33044 AN: 151956 Hom.: 4376 Cov.: 33

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.217 AC: 33043 AN: 152074 Hom.: 4377 Cov.: 33 AF XY: 0.218 AC XY: 16216 AN XY: 74322

African (AFR) AF: 0.0678 AC: 2814 AN: 41500

American (AMR) AF: 0.205 AC: 3135 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3472

East Asian (EAS) AF: 0.165 AC: 854 AN: 5180

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4810

European-Finnish (FIN) AF: 0.277 AC: 2921 AN: 10544

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19870 AN: 67970

Other (OTH) AF: 0.235 AC: 496 AN: 2114

Alfa AF: 0.236 Hom.: 603

Bravo AF: 0.205

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		-0.067
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: rs17277986; hg19: chr10-108758726;