rs2289404

Variant names:

• chr2-189771288-G-A
• rs2289404
• NM_016467.5:c.*479C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.*479C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000392349.9	NP_057551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9	c.*479C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_016467.5	ENSP00000376160.4

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.400 AC: 4 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.227 AC: 20 AN: 88

Other (OTH) AF: 0.300 AC: 3 AN: 10

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

African (AFR) AF: 0.473 AC: 13415 AN: 28378

American (AMR) AF: 0.488 AC: 3874 AN: 7942

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 741 AN: 1858

East Asian (EAS) AF: 0.437 AC: 1173 AN: 2682

South Asian (SAS) AF: 0.390 AC: 580 AN: 1486

European-Finnish (FIN) AF: 0.459 AC: 2061 AN: 4492

Middle Eastern (MID) AF: 0.452 AC: 75 AN: 166

European-Non Finnish (NFE) AF: 0.395 AC: 13397 AN: 33946

Other (OTH) AF: 0.446 AC: 473 AN: 1060

Alfa AF: 0.212 Hom.: 4607

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
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289404; hg19: chr2-190636014;