2-189778923-T-C

Variant names:

• chr2-189778923-T-C
• rs7606224
• NM_016467.5:c.175-3207A>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.175-3207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 152,212 control chromosomes in the GnomAD database, including 73,371 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 0.98 (73371 hom., cov: 29)
• Consequence: ORMDL1 NM_016467.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.175-3207A>G		intron_variant	Intron 3 of 4	ENST00000392349.9	NP_057551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9	c.175-3207A>G		intron_variant	Intron 3 of 4	1	NM_016467.5	ENSP00000376160.4

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149288 AN: 152094 Hom.: 73327 Cov.: 29

Gnomad AFR AF: 0.936

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.998

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.980

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.981 AC: 149390 AN: 152212 Hom.: 73371 Cov.: 29 AF XY: 0.982 AC XY: 73068 AN XY: 74426

African (AFR) AF: 0.936 AC: 38834 AN: 41484

American (AMR) AF: 0.995 AC: 15211 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5182 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4819 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10606 AN: 10606

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67989 AN: 68026

Other (OTH) AF: 0.981 AC: 2073 AN: 2114

Alfa AF: 0.989 Hom.: 23259

Bravo AF: 0.979

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-1.4
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: rs7606224; hg19: chr2-190643649;