chr11-121452568-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_003105.6(SORL1):c.237G>A(p.Arg79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,518,978 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.023 ( 61 hom., cov: 32)
Exomes 𝑓: 0.014 ( 205 hom. )
Consequence
SORL1
NM_003105.6 synonymous
NM_003105.6 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.00
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 11-121452568-G-A is Benign according to our data. Variant chr11-121452568-G-A is described in ClinVar as [Benign]. Clinvar id is 1210033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-121452568-G-A is described in Lovd as [Benign]. Variant chr11-121452568-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0234 (3564/152246) while in subpopulation AFR AF= 0.0377 (1565/41560). AF 95% confidence interval is 0.0361. There are 61 homozygotes in gnomad4. There are 1861 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 61 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORL1 | NM_003105.6 | c.237G>A | p.Arg79= | synonymous_variant | 1/48 | ENST00000260197.12 | |
SORL1-AS1 | NR_183636.1 | n.293+107C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORL1 | ENST00000260197.12 | c.237G>A | p.Arg79= | synonymous_variant | 1/48 | 1 | NM_003105.6 | P1 | |
SORL1 | ENST00000532451.1 | n.189G>A | non_coding_transcript_exon_variant | 1/15 | 1 | ||||
SORL1-AS1 | ENST00000501964.1 | n.339+107C>T | intron_variant, non_coding_transcript_variant | 2 | |||||
SORL1-AS1 | ENST00000529160.1 | n.245+107C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0234 AC: 3560AN: 152128Hom.: 61 Cov.: 32
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GnomAD3 exomes AF: 0.0133 AC: 1857AN: 139538Hom.: 20 AF XY: 0.0132 AC XY: 1050AN XY: 79376
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GnomAD4 exome AF: 0.0136 AC: 18607AN: 1366732Hom.: 205 Cov.: 31 AF XY: 0.0136 AC XY: 9174AN XY: 676176
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GnomAD4 genome ? AF: 0.0234 AC: 3564AN: 152246Hom.: 61 Cov.: 32 AF XY: 0.0250 AC XY: 1861AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at