10-106793863-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052918.5(SORCS1):​c.727-17171G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,036 control chromosomes in the GnomAD database, including 6,961 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 0.30 ( 6961 hom., cov: 32)

Consequence

SORCS1
NM_052918.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SORCS1NM_052918.5 linkuse as main transcriptc.727-17171G>C intron_variant ENST00000263054.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SORCS1ENST00000263054.11 linkuse as main transcriptc.727-17171G>C intron_variant 1 NM_052918.5 P1Q8WY21-1

Frequencies

GnomAD3 genomes
AF:
0.299
AC:
45405
AN:
151918
Hom.:
6948
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.317
Gnomad AMI
AF:
0.330
Gnomad AMR
AF:
0.254
Gnomad ASJ
AF:
0.257
Gnomad EAS
AF:
0.141
Gnomad SAS
AF:
0.260
Gnomad FIN
AF:
0.316
Gnomad MID
AF:
0.220
Gnomad NFE
AF:
0.313
Gnomad OTH
AF:
0.269
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.299
AC:
45472
AN:
152036
Hom.:
6961
Cov.:
32
AF XY:
0.296
AC XY:
22020
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.317
Gnomad4 AMR
AF:
0.254
Gnomad4 ASJ
AF:
0.257
Gnomad4 EAS
AF:
0.141
Gnomad4 SAS
AF:
0.258
Gnomad4 FIN
AF:
0.316
Gnomad4 NFE
AF:
0.313
Gnomad4 OTH
AF:
0.275
Alfa
AF:
0.171
Hom.:
332
Bravo
AF:
0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
1.9
DANN
Benign
0.69

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11193054; hg19: chr10-108553621; API