NM_052918.5:c.727-10507T>C

Variant names:

• chr10-106787199-A-G
• rs7091546
• NM_052918.5:c.727-10507T>C

Variant summary

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

The NM_052918.5(SORCS1):​c.727-10507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,122 control chromosomes in the GnomAD database, including 4,379 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 0.23 (4379 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.727-10507T>C		intron_variant	Intron 3 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.727-10507T>C		intron_variant	Intron 3 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34362 AN: 152004 Hom.: 4375 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.226 AC: 34390 AN: 152122 Hom.: 4379 Cov.: 32 AF XY: 0.226 AC XY: 16769 AN XY: 74346

African (AFR) AF: 0.132 AC: 5473 AN: 41552

American (AMR) AF: 0.213 AC: 3256 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3468

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5174

South Asian (SAS) AF: 0.197 AC: 948 AN: 4810

European-Finnish (FIN) AF: 0.325 AC: 3432 AN: 10556

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.288 AC: 19604 AN: 67972

Other (OTH) AF: 0.219 AC: 462 AN: 2114

Alfa AF: 0.250 Hom.: 4043

Bravo AF: 0.211

Asia WGS AF: 0.143 AC: 501 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.75
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: rs7091546; hg19: chr10-108546957;