10-106807618-G-C

Position:

• chr10-106807618-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_052918.5(SORCS1):​c.726+21956C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,110 control chromosomes in the GnomAD database, including 8,198 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 0.32 (8198 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.726+21956C>G		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.726+21956C>G		intron_variant		1	NM_052918.5	ENSP00000263054	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49278 AN: 151992 Hom.: 8184 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.324 AC: 49340 AN: 152110 Hom.: 8198 Cov.: 33 AF XY: 0.320 AC XY: 23820 AN XY: 74360

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.298

Alfa AF: 0.169 Hom.: 308

Bravo AF: 0.325

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.68

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: rs1572456; hg19: chr10-108567376;