chr2-189771288-G-A

Position:

• chr2-189771288-G-A

Variant summary

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

The NM_016467.5(ORMDL1):​c.*479C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 82,548 control chromosomes in the GnomAD database, including 4,566 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 0.44 (4564 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: ORMDL1 NM_016467.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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 (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.*479C>T		3_prime_UTR_variant	5/5	ENST00000392349.9	NP_057551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9	c.*479C>T		3_prime_UTR_variant	5/5	1	NM_016467.5	ENSP00000376160	P1
ORMDL1	ENST00000325795.7	c.*479C>T		3_prime_UTR_variant	3/3	1		ENSP00000326869	P1
ORMDL1	ENST00000392350.7	c.*479C>T		3_prime_UTR_variant	4/4	1		ENSP00000376161	P1
ORMDL1	ENST00000496543.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 35875 AN: 82328 Hom.: 4553 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.234 AC: 30 AN: 128 Hom.: 2 Cov.: 0 AF XY: 0.231 AC XY: 18 AN XY: 78

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.436 AC: 35913 AN: 82420 Hom.: 4564 Cov.: 33 AF XY: 0.436 AC XY: 17340 AN XY: 39746

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.446

Alfa AF: 0.208 Hom.: 3270

Bravo AF: 0.244

Asia WGS AF: 0.203 AC: 705 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.74

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: rs2289404; hg19: chr2-190636014;