rs1023023

Positions:

• chr10-106978955-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052918.5(SORCS1):​c.559-22375T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,136 control chromosomes in the GnomAD database, including 4,621 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 0.22 (4621 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-22375T>C		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.559-22375T>C		intron_variant		1	NM_052918.5	ENSP00000263054	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34027 AN: 152018 Hom.: 4622 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.224 AC: 34023 AN: 152136 Hom.: 4621 Cov.: 32 AF XY: 0.225 AC XY: 16741 AN XY: 74360

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.240

Alfa AF: 0.242 Hom.: 527

Bravo AF: 0.210

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1023023; hg19: chr10-108738713;