11-121452635-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_003105.6(SORL1):c.285+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,440,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
SORL1
NM_003105.6 intron
NM_003105.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.518
Genes affected
SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 11-121452635-C-T is Benign according to our data. Variant chr11-121452635-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1936071.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00000621 (8/1287668) while in subpopulation AFR AF= 0.00023 (6/26100). AF 95% confidence interval is 0.0000992. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORL1 | NM_003105.6 | c.285+19C>T | intron_variant | ENST00000260197.12 | |||
SORL1-AS1 | NR_183636.1 | n.293+40G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORL1 | ENST00000260197.12 | c.285+19C>T | intron_variant | 1 | NM_003105.6 | P1 | |||
SORL1-AS1 | ENST00000501964.1 | n.339+40G>A | intron_variant, non_coding_transcript_variant | 2 | |||||
SORL1 | ENST00000532451.1 | n.237+19C>T | intron_variant, non_coding_transcript_variant | 1 | |||||
SORL1-AS1 | ENST00000529160.1 | n.245+40G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000621 AC: 8AN: 1287668Hom.: 0 Cov.: 30 AF XY: 0.00000477 AC XY: 3AN XY: 629132
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 19, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at