Genetic Variant ORMDL1:c.*479C>T (chr2-189771288-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

12 publications found

Variant links:

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]

ORMDL1 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ORMDL1	NM_016467.5	MANE Select	c.*479C>T	3_prime_UTR	Exon 5 of 5	NP_057551.1
ORMDL1	NM_001128150.2		c.*479C>T	3_prime_UTR	Exon 4 of 4	NP_001121622.1
ORMDL1	NM_001371385.1		c.455+486C>T	intron	N/A	NP_001358314.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ORMDL1	ENST00000392349.9	TSL:1 MANE Select	c.*479C>T	3_prime_UTR	Exon 5 of 5	ENSP00000376160.4
ORMDL1	ENST00000325795.7	TSL:1	c.*479C>T	3_prime_UTR	Exon 3 of 3	ENSP00000326869.3
ORMDL1	ENST00000392350.7	TSL:1	c.*479C>T	3_prime_UTR	Exon 4 of 4	ENSP00000376161.3

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

35875

AN:

82328

Hom.:

4553

Cov.:

show subpopulations

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:

AN:

128

Hom.:

Cov.:

AF XY:

0.231

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.400

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.436

AC:

35913

AN:

82420

Hom.:

4564

Cov.:

AF XY:

0.436

AC XY:

17340

AN XY:

39746

show subpopulations

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:

AN:

166

European-Non Finnish (NFE)

AF:

0.395

AC:

13397

AN:

33946

Other (OTH)

AF:

0.446

AC:

473

AN:

1060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1416

2832

4249

5665

7081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

(source)

DANN

Benign

0.74

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over