rs6942

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-189771685-C-A
• chr2-189771685-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016467.5(ORMDL1):​c.*82G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ORMDL1 NM_016467.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 21 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016467.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORMDL1	NM_016467.5	MANE Select	c.*82G>T		3_prime_UTR	Exon 5 of 5	NP_057551.1
	ORMDL1	NM_001128150.2		c.*82G>T		3_prime_UTR	Exon 4 of 4	NP_001121622.1
	ORMDL1	NM_001371385.1		c.455+89G>T		intron	N/A	NP_001358314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORMDL1	ENST00000392349.9	TSL:1 MANE Select	c.*82G>T		3_prime_UTR	Exon 5 of 5	ENSP00000376160.4
	ORMDL1	ENST00000325795.7	TSL:1	c.*82G>T		3_prime_UTR	Exon 3 of 3	ENSP00000326869.3
	ORMDL1	ENST00000392350.7	TSL:1	c.*82G>T		3_prime_UTR	Exon 4 of 4	ENSP00000376161.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1075596 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 537608

African (AFR) AF: 0.00 AC: 0 AN: 22724

American (AMR) AF: 0.00 AC: 0 AN: 21734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17886

East Asian (EAS) AF: 0.00 AC: 0 AN: 33778

South Asian (SAS) AF: 0.00 AC: 0 AN: 54100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 829356

Other (OTH) AF: 0.00 AC: 0 AN: 45912

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.094

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: rs6942; hg19: chr2-190636411;