10-106793863-C-G

Variant names:

• chr10-106793863-C-G
• rs11193054
• NM_052918.5:c.727-17171G>C

Variant summary

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

The NM_001387556.1(SORCS1):​c.727-17171G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,036 control chromosomes in the GnomAD database, including 6,961 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 0.30 (6961 hom., cov: 32)
• Consequence: SORCS1 NM_001387556.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387556.1. 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.727-17171G>C		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.727-17171G>C		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.727-17171G>C		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.727-17171G>C		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45405 AN: 151918 Hom.: 6948 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.299 AC: 45472 AN: 152036 Hom.: 6961 Cov.: 32 AF XY: 0.296 AC XY: 22020 AN XY: 74290

African (AFR) AF: 0.317 AC: 13144 AN: 41478

American (AMR) AF: 0.254 AC: 3883 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3468

East Asian (EAS) AF: 0.141 AC: 732 AN: 5180

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4820

European-Finnish (FIN) AF: 0.316 AC: 3333 AN: 10546

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21294 AN: 67952

Other (OTH) AF: 0.275 AC: 579 AN: 2108

Alfa AF: 0.171 Hom.: 332

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-1.2
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: rs11193054; hg19: chr10-108553621;