rs17608925

Positions:

• chr17-39926578-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139280.4(ORMDL3):​c.-23+906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 166,448 control chromosomes in the GnomAD database, including 910 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 0.097 (827 hom., cov: 32)
  • Exomes 𝑓: 0.11 (83 hom.)
• Consequence: ORMDL3 NM_139280.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORMDL3	NM_139280.4	c.-23+906A>G		intron_variant		ENST00000304046.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORMDL3	ENST00000304046.7	c.-23+906A>G		intron_variant		1	NM_139280.4	P1

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14756 AN: 152136 Hom.: 825 Cov.: 32

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0962

GnomAD4 exome AF: 0.110 AC: 1558 AN: 14194 Hom.: 83 Cov.: 0 AF XY: 0.109 AC XY: 770 AN XY: 7042

Gnomad4 AFR exome AF: 0.0395

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.0969 AC: 14758 AN: 152254 Hom.: 827 Cov.: 32 AF XY: 0.102 AC XY: 7570 AN XY: 74434

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0808

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.101 Hom.: 820

Bravo AF: 0.0881

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.86

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: rs17608925; hg19: chr17-38082831;