Genetic Variant NM_052918.5:c.559-79037T>C (chr10-107035617-A-G) – 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.559-79037T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,034 control chromosomes in the GnomAD database, including 17,969 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 0.48 ( 17969 hom., cov: 32)

Consequence

SORCS1
NM_052918.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.985

Publications

12 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5 link	c.559-79037T>C		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.559-79037T>C		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5		Q8WY21-1
ENSG00000294532	ENST00000724189.1 link	n.119+9516A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73605

AN:

151916

Hom.:

17952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.473

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

GnomAD4 genome

AF:

0.485

AC:

73679

AN:

152034

Hom.:

17969

Cov.:

AF XY:

0.490

AC XY:

36447

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.473

AC:

19620

AN:

41478

American (AMR)

AF:

0.510

AC:

7788

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1583

AN:

3470

East Asian (EAS)

AF:

0.646

AC:

3338

AN:

5166

South Asian (SAS)

AF:

0.526

AC:

2532

AN:

4818

European-Finnish (FIN)

AF:

0.529

AC:

5571

AN:

10532

Middle Eastern (MID)

AF:

0.390

AC:

114

AN:

292

European-Non Finnish (NFE)

AF:

0.464

AC:

31535

AN:

67978

Other (OTH)

AF:

0.478

AC:

1009

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1945

3891

5836

7782

9727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.470

Hom.:

76098

Bravo

AF:

0.482

Asia WGS

AF:

0.572

AC:

1988

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

(source)

DANN

Benign

0.32

PhyloP100

0.98

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