rs12603332

chr17-39926554-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_139280.4(ORMDL3):c.-23+930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 155,016 control chromosomes in the GnomAD database, including 19,086 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 0.49 (18730 hom., cov: 32)
  • Exomes 𝑓: 0.49 (356 hom.)
• Consequence: ORMDL3 NM_139280.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORMDL3	NM_139280.4	c.-23+930A>G		intron_variant		ENST00000304046.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORMDL3	ENST00000304046.7	c.-23+930A>G		intron_variant		1	NM_139280.4	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74583 AN: 151934 Hom.: 18737 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.485 AC: 1439 AN: 2964 Hom.: 356 Cov.: 0 AF XY: 0.492 AC XY: 728 AN XY: 1480

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.579

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.490 AC: 74578 AN: 152052 Hom.: 18730 Cov.: 32 AF XY: 0.490 AC XY: 36432 AN XY: 74302

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.519

Alfa AF: 0.514 Hom.: 21145

Bravo AF: 0.500

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	17
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12603332; hg19: chr17-38082807;