rs45601540
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_021267.5(CERS1):c.492C>T(p.Tyr164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00905 in 1,613,654 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0068 ( 10 hom., cov: 31)
Exomes 𝑓: 0.0093 ( 90 hom. )
Consequence
CERS1
NM_021267.5 synonymous
NM_021267.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.48
Genes affected
CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]
GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 19-18884185-G-A is Benign according to our data. Variant chr19-18884185-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.48 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERS1 | NM_021267.5 | c.492C>T | p.Tyr164= | synonymous_variant | 3/8 | ENST00000623882.4 | |
GDF1 | NM_001492.6 | c.-831C>T | 5_prime_UTR_variant | 3/8 | ENST00000247005.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERS1 | ENST00000623882.4 | c.492C>T | p.Tyr164= | synonymous_variant | 3/8 | 1 | NM_021267.5 | P2 | |
GDF1 | ENST00000247005.8 | c.-831C>T | 5_prime_UTR_variant | 3/8 | 1 | NM_001492.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00678 AC: 1031AN: 152020Hom.: 10 Cov.: 31
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GnomAD3 exomes AF: 0.00680 AC: 1674AN: 246002Hom.: 17 AF XY: 0.00685 AC XY: 917AN XY: 133800
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GnomAD4 exome AF: 0.00929 AC: 13571AN: 1461516Hom.: 90 Cov.: 31 AF XY: 0.00905 AC XY: 6582AN XY: 727026
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GnomAD4 genome ? AF: 0.00678 AC: 1031AN: 152138Hom.: 10 Cov.: 31 AF XY: 0.00687 AC XY: 511AN XY: 74382
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | CERS1: BP4, BP7, BS2 - |
Progressive myoclonic epilepsy type 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at