dbSNP rs17608925: ORMDL3:c.-23+906A>G (chr17-39926578-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_139280.4(ORMDL3):c.-23+906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 166,448 control chromosomes in the GnomAD database, including 910 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 0.097 ( 827 hom., cov: 32)

Exomes 𝑓: 0.11 ( 83 hom. )

Consequence

ORMDL3
NM_139280.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

19 publications found

Variant links:

Genes affected

ORMDL3 (HGNC:16038): (ORMDL sphingolipid biosynthesis regulator 3) Involved in ceramide metabolic process. Acts upstream of or within several processes, including negative regulation of B cell apoptotic process; negative regulation of ceramide biosynthetic process; and positive regulation of protein localization to nucleus. Located in endoplasmic reticulum. Part of SPOTS complex. [provided by Alliance of Genome Resources, Apr 2022]

ORMDL3 links:

LOC124903999 (HGNC:):

LOC124903999 links:

Genome browser will be placed here

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=-0.68).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORMDL3	NM_139280.4 link	c.-23+906A>G		intron_variant	Intron 1 of 3	ENST00000304046.7	NP_644809.1	Q8N138-1A0A024R1W6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORMDL3	ENST00000304046.7 link	c.-23+906A>G		intron_variant	Intron 1 of 3	1	NM_139280.4	ENSP00000304858.2		Q8N138-1

Frequencies

GnomAD3 genomes

AF:

0.0970

AC:

14756

AN:

152136

Hom.:

825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0808

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0962

GnomAD4 exome

AF:

0.110

AC:

1558

AN:

14194

Hom.:

Cov.:

AF XY:

0.109

AC XY:

770

AN XY:

7042

show subpopulations

African (AFR)

AF:

0.0395

AC:

AN:

228

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0882

AC:

AN:

102

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.113

AC:

AN:

240

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

1450

AN:

13056

Other (OTH)

AF:

0.117

AC:

AN:

470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0969

AC:

14758

AN:

152254

Hom.:

827

Cov.:

AF XY:

0.102

AC XY:

7570

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0573

AC:

2380

AN:

41564

American (AMR)

AF:

0.114

AC:

1742

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

384

AN:

3470

East Asian (EAS)

AF:

0.0808

AC:

418

AN:

5172

South Asian (SAS)

AF:

0.156

AC:

752

AN:

4824

European-Finnish (FIN)

AF:

0.169

AC:

1789

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6889

AN:

68016

Other (OTH)

AF:

0.0956

AC:

202

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

687

1374

2061

2748

3435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0962

Hom.:

1161

Bravo

AF:

0.0881

Asia WGS

AF:

0.100

AC:

349

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.098

PromoterAI

0.12

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over