dbSNP rs12359404: SORCS1:c.*2989G>A (chr10-106574431-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052918.5(SORCS1):c.*2989G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,582 control chromosomes in the GnomAD database, including 193 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 0.041 ( 193 hom., cov: 32)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

SORCS1
NM_052918.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.67

Publications

5 publications found

Variant links:

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)

SORCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5 link	c.*2989G>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000263054.11	NP_443150.3	Q8WY21-1B3KWN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11 link	c.*2989G>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_052918.5	ENSP00000263054.5		Q8WY21-1

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6197

AN:

152004

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0676

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0893

Gnomad FIN

AF:

0.0410

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0397

GnomAD4 exome

AF:

0.0261

AC:

AN:

460

Hom.:

Cov.:

AF XY:

0.0393

AC XY:

AN XY:

280

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0280

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0408

AC:

6208

AN:

152122

Hom.:

193

Cov.:

AF XY:

0.0425

AC XY:

3159

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0676

AC:

2805

AN:

41486

American (AMR)

AF:

0.0206

AC:

315

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3472

East Asian (EAS)

AF:

0.141

AC:

726

AN:

5162

South Asian (SAS)

AF:

0.0889

AC:

428

AN:

4812

European-Finnish (FIN)

AF:

0.0410

AC:

434

AN:

10578

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1274

AN:

68016

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

297

595

892

1190

1487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0256

Hom.:

100

Bravo

AF:

0.0393

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.022

(source)

DANN

Benign

0.72

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over