rs1472050

Variant summary

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

The NM_014978.3(SORCS3):​c.627+93059A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,172 control chromosomes in the GnomAD database, including 4,246 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 0.23 ( 4246 hom., cov: 32)

Consequence

SORCS3
NM_014978.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
SORCS3 (HGNC:16699): (sortilin related VPS10 domain containing receptor 3) This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SORCS3NM_014978.3 linkuse as main transcriptc.627+93059A>C intron_variant ENST00000369701.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SORCS3ENST00000369701.8 linkuse as main transcriptc.627+93059A>C intron_variant 1 NM_014978.3 P1

Frequencies

GnomAD3 genomes
AF:
0.231
AC:
35122
AN:
152054
Hom.:
4232
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.208
Gnomad AMI
AF:
0.138
Gnomad AMR
AF:
0.300
Gnomad ASJ
AF:
0.166
Gnomad EAS
AF:
0.249
Gnomad SAS
AF:
0.334
Gnomad FIN
AF:
0.197
Gnomad MID
AF:
0.185
Gnomad NFE
AF:
0.231
Gnomad OTH
AF:
0.226
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.231
AC:
35154
AN:
152172
Hom.:
4246
Cov.:
32
AF XY:
0.231
AC XY:
17184
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.208
Gnomad4 AMR
AF:
0.301
Gnomad4 ASJ
AF:
0.166
Gnomad4 EAS
AF:
0.248
Gnomad4 SAS
AF:
0.334
Gnomad4 FIN
AF:
0.197
Gnomad4 NFE
AF:
0.231
Gnomad4 OTH
AF:
0.234
Alfa
AF:
0.226
Hom.:
507
Bravo
AF:
0.234
Asia WGS
AF:
0.348
AC:
1207
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
10
DANN
Benign
0.79

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: rs1472050; hg19: chr10-106494771; API