10-106650827-C-T

Variant names:

• chr10-106650827-C-T
• rs11192998
• NM_052918.5:c.2475+1555G>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.2475+1555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,030 control chromosomes in the GnomAD database, including 5,342 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 0.24 (5342 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• 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)

ENSG00000287047 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.2475+1555G>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.2475+1555G>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.2475+1555G>A		intron	N/A	NP_001013049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.2475+1555G>A		intron	N/A	ENSP00000263054.5
	SORCS1	ENST00000369698.6	TSL:5	c.1206+1555G>A		intron	N/A	ENSP00000358712.2
	ENSG00000287047	ENST00000662495.2		n.403+1682C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36298 AN: 151912 Hom.: 5336 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.239 AC: 36338 AN: 152030 Hom.: 5342 Cov.: 32 AF XY: 0.242 AC XY: 18024 AN XY: 74344

African (AFR) AF: 0.385 AC: 15945 AN: 41460

American (AMR) AF: 0.160 AC: 2439 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2678 AN: 5158

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1847 AN: 10568

Middle Eastern (MID) AF: 0.179 AC: 52 AN: 290

European-Non Finnish (NFE) AF: 0.158 AC: 10764 AN: 67974

Other (OTH) AF: 0.205 AC: 432 AN: 2108

Alfa AF: 0.186 Hom.: 1684

Bravo AF: 0.243

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		-0.45
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: rs11192998; hg19: chr10-108410585;