Genetic Variant SORCS1:c.559-77450A>G (chr10-107034030-T-C) – 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.559-77450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,992 control chromosomes in the GnomAD database, including 9,793 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 0.36 ( 9793 hom., cov: 32)

Consequence

SORCS1
NM_052918.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.811

Publications

4 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:

ENSG00000294532 (HGNC:):

ENSG00000294532 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=-0.53).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5 link	c.559-77450A>G		intron_variant	Intron 1 of 25	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.559-77450A>G		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5		Q8WY21-1
ENSG00000294532	ENST00000724189.1 link	n.119+7929T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54404

AN:

151874

Hom.:

9783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.360

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

GnomAD4 genome

AF:

0.358

AC:

54462

AN:

151992

Hom.:

9793

Cov.:

AF XY:

0.362

AC XY:

26862

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.333

AC:

13799

AN:

41440

American (AMR)

AF:

0.411

AC:

6279

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1241

AN:

3472

East Asian (EAS)

AF:

0.314

AC:

1618

AN:

5158

South Asian (SAS)

AF:

0.345

AC:

1663

AN:

4820

European-Finnish (FIN)

AF:

0.407

AC:

4299

AN:

10558

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24214

AN:

67964

Other (OTH)

AF:

0.363

AC:

765

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1856

3711

5567

7422

9278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.341

Hom.:

6495

Bravo

AF:

0.359

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.81

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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10-107034030-T-C

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