chr2-189775189-A-C

Position:

• chr2-189775189-A-C

Variant summary

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

The NM_016467.5(ORMDL1):​c.326+376T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 156,426 control chromosomes in the GnomAD database, including 4,170 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 0.23 (4108 hom., cov: 32)
  • Exomes 𝑓: 0.17 (62 hom.)
• Consequence: ORMDL1 NM_016467.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

Genes affected

ORMDL1 (HGNC:16036): (ORMDL sphingolipid biosynthesis regulator 1) Involved in ceramide metabolic process. Acts upstream of or within negative regulation of ceramide biosynthetic process. Located in endoplasmic reticulum membrane. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.326+376T>G		intron_variant		ENST00000392349.9	NP_057551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9	c.326+376T>G		intron_variant		1	NM_016467.5	ENSP00000376160	P1
ORMDL1	ENST00000325795.7	c.326+376T>G		intron_variant		1		ENSP00000326869	P1
ORMDL1	ENST00000392350.7	c.326+376T>G		intron_variant		1		ENSP00000376161	P1
ORMDL1	ENST00000409519.5	c.*372T>G		3_prime_UTR_variant	3/3	3		ENSP00000386253

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34461 AN: 151972 Hom.: 4100 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.170 AC: 736 AN: 4336 Hom.: 62 Cov.: 0 AF XY: 0.163 AC XY: 367 AN XY: 2250

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.227 AC: 34488 AN: 152090 Hom.: 4108 Cov.: 32 AF XY: 0.225 AC XY: 16744 AN XY: 74364

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.217

Alfa AF: 0.196 Hom.: 2963

Bravo AF: 0.232

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.62

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: rs3791767; hg19: chr2-190639915;