2-189771685-C-G

Variant names:

• chr2-189771685-C-G
• rs6942
• NM_016467.5:c.*82G>C

Variant summary

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

The NM_016467.5(ORMDL1):​c.*82G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,225,056 control chromosomes in the GnomAD database, including 316,012 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 0.59 (30124 hom., cov: 33)
  • Exomes 𝑓: 0.73 (285888 hom.)
• Consequence: ORMDL1 NM_016467.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.*82G>C		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	c.*82G>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_016467.5	ENSP00000376160.4
ORMDL1	ENST00000325795	c.*82G>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000326869.3
ORMDL1	ENST00000392350	c.*82G>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000376161.3
ORMDL1	ENST00000496543.1	n.349G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89880 AN: 152030 Hom.: 30104 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.725 AC: 778395 AN: 1072910 Hom.: 285888 Cov.: 13 AF XY: 0.727 AC XY: 390040 AN XY: 536278

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.702

Gnomad4 NFE exome AF: 0.740

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.591 AC: 89912 AN: 152146 Hom.: 30124 Cov.: 33 AF XY: 0.595 AC XY: 44281 AN XY: 74404

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.624

Alfa AF: 0.644 Hom.: 4224

Bravo AF: 0.575

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6942; hg19: chr2-190636411; COSMIC: COSV57877686; COSMIC: COSV57877686;