rs3791767

Variant names:

• chr2-189775189-A-C
• rs3791767
• NM_016467.5:c.326+376T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-189775189-A-C
• chr2-189775189-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORMDL1	NM_016467.5	MANE Select	c.326+376T>G		intron	N/A	NP_057551.1	Q9P0S3
	ORMDL1	NM_001371385.1		c.326+376T>G		intron	N/A	NP_001358314.1	A0ABB0MVM0
	ORMDL1	NM_001371386.1		c.326+376T>G		intron	N/A	NP_001358315.1	A0ABB0MVM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORMDL1	ENST00000392349.9	TSL:1 MANE Select	c.326+376T>G		intron	N/A	ENSP00000376160.4	Q9P0S3
	ORMDL1	ENST00000325795.7	TSL:1	c.326+376T>G		intron	N/A	ENSP00000326869.3	Q9P0S3
	ORMDL1	ENST00000392350.7	TSL:1	c.326+376T>G		intron	N/A	ENSP00000376161.3	Q9P0S3

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

African (AFR) AF: 0.227 AC: 29 AN: 128

American (AMR) AF: 0.182 AC: 51 AN: 280

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 28 AN: 138

East Asian (EAS) AF: 0.227 AC: 30 AN: 132

South Asian (SAS) AF: 0.116 AC: 31 AN: 268

European-Finnish (FIN) AF: 0.123 AC: 17 AN: 138

Middle Eastern (MID) AF: 0.100 AC: 2 AN: 20

European-Non Finnish (NFE) AF: 0.168 AC: 508 AN: 3024

Other (OTH) AF: 0.192 AC: 40 AN: 208

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

African (AFR) AF: 0.285 AC: 11828 AN: 41476

American (AMR) AF: 0.250 AC: 3818 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 741 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1172 AN: 5176

South Asian (SAS) AF: 0.172 AC: 827 AN: 4822

European-Finnish (FIN) AF: 0.194 AC: 2058 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13386 AN: 67962

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.210 Hom.: 6589

Bravo AF: 0.232

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		0.39
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: rs3791767; hg19: chr2-190639915;