chr19-18869404-A-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001387440.1(CERS1):c.*1173T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CERS1
NM_001387440.1 3_prime_UTR
NM_001387440.1 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.701
Genes affected
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GDF1 | NM_001492.6 | c.326-14T>A | intron_variant | Intron 7 of 7 | ENST00000247005.8 | NP_001483.3 | ||
| CERS1 | NM_021267.5 | c.*595-14T>A | intron_variant | Intron 7 of 7 | ENST00000623882.4 | NP_067090.1 | ||
| CERS1 | NM_001387440.1 | c.*1173T>A | 3_prime_UTR_variant | Exon 7 of 7 | NP_001374369.1 | |||
| GDF1 | NM_001387438.1 | c.326-14T>A | intron_variant | Intron 4 of 4 | NP_001374367.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
28
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.27e-7 AC: 1AN: 1376258Hom.: 0 Cov.: 45 AF XY: 0.00000147 AC XY: 1AN XY: 679268
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1376258
Hom.:
Cov.:
45
AF XY:
AC XY:
1
AN XY:
679268
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
28
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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