Genetic Variant NM_016467.5:c.*82G>C (chr2-189771685-C-G) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

21 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=-0.66).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 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.*82G>C	3_prime_UTR	Exon 5 of 5	NP_057551.1
ORMDL1	NM_001128150.2		c.*82G>C	3_prime_UTR	Exon 4 of 4	NP_001121622.1
ORMDL1	NM_001371385.1		c.455+89G>C	intron	N/A	NP_001358314.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89880

AN:

152030

Hom.:

30104

Cov.:

show subpopulations

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.:

AF XY:

0.727

AC XY:

390040

AN XY:

536278

show subpopulations

African (AFR)

AF:

0.217

AC:

4933

AN:

22692

American (AMR)

AF:

0.716

AC:

15505

AN:

21662

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

13293

AN:

17854

East Asian (EAS)

AF:

0.715

AC:

24115

AN:

33732

South Asian (SAS)

AF:

0.760

AC:

40998

AN:

53944

European-Finnish (FIN)

AF:

0.702

AC:

31855

AN:

45352

Middle Eastern (MID)

AF:

0.663

AC:

3088

AN:

4660

European-Non Finnish (NFE)

AF:

0.740

AC:

612269

AN:

827206

Other (OTH)

AF:

0.706

AC:

32339

AN:

45808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9701

19402

29103

38804

48505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14430

28860

43290

57720

72150

<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:

0.591

AC:

89912

AN:

152146

Hom.:

30124

Cov.:

AF XY:

0.595

AC XY:

44281

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.244

AC:

10123

AN:

41504

American (AMR)

AF:

0.667

AC:

10195

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

2563

AN:

3468

East Asian (EAS)

AF:

0.717

AC:

3718

AN:

5184

South Asian (SAS)

AF:

0.758

AC:

3662

AN:

4830

European-Finnish (FIN)

AF:

0.699

AC:

7406

AN:

10596

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.735

AC:

49972

AN:

67954

Other (OTH)

AF:

0.624

AC:

1319

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1533

3066

4599

6132

7665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.644

Hom.:

4224

Bravo

AF:

0.575

Asia WGS

AF:

0.686

AC:

2387

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.8

(source)

DANN

Benign

0.75

PhyloP100

0.094

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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