rs7907713

Variant names:

• chr10-107169575-G-A
• rs7907713
• XM_017015617.1:c.3+11489C>T

Variant summary

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

The XM_017015617.1(SORCS1):​c.3+11489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,970 control chromosomes in the GnomAD database, including 4,042 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 (4042 hom., cov: 32)
• Consequence: SORCS1 XM_017015617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• 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 = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	XM_017015617.1	c.3+11489C>T		intron_variant	Intron 1 of 26		XP_016871106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34622 AN: 151850 Hom.: 4028 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.228 AC: 34672 AN: 151970 Hom.: 4042 Cov.: 32 AF XY: 0.227 AC XY: 16840 AN XY: 74298

African (AFR) AF: 0.275 AC: 11389 AN: 41442

American (AMR) AF: 0.189 AC: 2881 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 685 AN: 3464

East Asian (EAS) AF: 0.0992 AC: 513 AN: 5170

South Asian (SAS) AF: 0.151 AC: 728 AN: 4816

European-Finnish (FIN) AF: 0.247 AC: 2608 AN: 10548

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15224 AN: 67944

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.219 Hom.: 13355

Bravo AF: 0.225

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7907713; hg19: chr10-108929333;