rs607437

Variant names:

• chr10-107120697-A-G
• rs607437
• NM_052918.5:c.558+43272T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-107120697-A-G
• chr10-107120697-A-T

Variant summary

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

The NM_052918.5(SORCS1):​c.558+43272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,076 control chromosomes in the GnomAD database, including 28,376 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 0.61 (28376 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 7 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.558+43272T>C		intron_variant	Intron 1 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+43272T>C		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91952 AN: 151958 Hom.: 28338 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.605 AC: 92037 AN: 152076 Hom.: 28376 Cov.: 32 AF XY: 0.600 AC XY: 44579 AN XY: 74324

African (AFR) AF: 0.710 AC: 29450 AN: 41496

American (AMR) AF: 0.507 AC: 7745 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2370 AN: 5164

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4822

European-Finnish (FIN) AF: 0.543 AC: 5737 AN: 10562

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40368 AN: 67988

Other (OTH) AF: 0.579 AC: 1220 AN: 2106

Alfa AF: 0.595 Hom.: 118228

Bravo AF: 0.611

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.38
PhyloP100		0.37
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: rs607437; hg19: chr10-108880455;