rs9900885
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_139280.4(ORMDL3):c.-23+686T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 986,156 control chromosomes in the GnomAD database, including 6 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 0.0045 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 4 hom. )
Consequence
ORMDL3
NM_139280.4 intron
NM_139280.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0530
Genes affected
ORMDL3 (HGNC:16038): (ORMDL sphingolipid biosynthesis regulator 3) Involved in ceramide metabolic process. Acts upstream of or within several processes, including negative regulation of B cell apoptotic process; negative regulation of ceramide biosynthetic process; and positive regulation of protein localization to nucleus. Located in endoplasmic reticulum. Part of SPOTS complex. [provided by Alliance of Genome Resources, Apr 2022]
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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=-0.82).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000354 (295/833876) while in subpopulation AFR AF= 0.0168 (266/15808). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4_exome. There are 132 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 686 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ORMDL3 | NM_139280.4 | c.-23+686T>C | intron_variant | ENST00000304046.7 | |||
LOC124903999 | XR_007065750.1 | n.43+36A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ORMDL3 | ENST00000304046.7 | c.-23+686T>C | intron_variant | 1 | NM_139280.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00450 AC: 685AN: 152162Hom.: 2 Cov.: 32
GnomAD3 genomes
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32
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GnomAD4 exome AF: 0.000354 AC: 295AN: 833876Hom.: 4 Cov.: 29 AF XY: 0.000343 AC XY: 132AN XY: 385310
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GnomAD4 genome ? AF: 0.00450 AC: 686AN: 152280Hom.: 2 Cov.: 32 AF XY: 0.00451 AC XY: 336AN XY: 74452
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ClinVar
Not reported inComputational scores
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Name
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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