chr10-106794833-T-C

Variant names:

• chr10-106794833-T-C
• rs10509823
• NM_052918.5:c.727-18141A>G

Variant summary

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

The NM_052918.5(SORCS1):​c.727-18141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,018 control chromosomes in the GnomAD database, including 4,607 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 (4607 hom., cov: 31)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 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.727-18141A>G		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.727-18141A>G		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.727-18141A>G		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.727-18141A>G		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36011 AN: 151900 Hom.: 4602 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.237 AC: 36052 AN: 152018 Hom.: 4607 Cov.: 31 AF XY: 0.236 AC XY: 17540 AN XY: 74278

African (AFR) AF: 0.174 AC: 7234 AN: 41476

American (AMR) AF: 0.218 AC: 3324 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3470

East Asian (EAS) AF: 0.0329 AC: 170 AN: 5166

South Asian (SAS) AF: 0.198 AC: 956 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3249 AN: 10528

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19603 AN: 67974

Other (OTH) AF: 0.221 AC: 466 AN: 2106

Alfa AF: 0.255 Hom.: 4347

Bravo AF: 0.224

Asia WGS AF: 0.143 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-1.7
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: rs10509823; hg19: chr10-108554591;