Genetic Variant ORM2:p.Arg38Trp (chr9-114330016-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000608.4(ORM2):c.112C>T(p.Arg38Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,580,670 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

ORM2
NM_000608.4 missense, splice_region

Scores

Splicing: ADA: 0.001561

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

Publications

0 publications found

Variant links:

Genes affected

ORM2 (HGNC:8499): (orosomucoid 2) This gene encodes a key acute phase plasma protein. Because of its increase due to acute inflammation, this protein is classified as an acute-phase reactant. The specific function of this protein has not yet been determined; however, it may be involved in aspects of immunosuppression. [provided by RefSeq, Jul 2008]

ORM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009924918).

BP6

Variant 9-114330016-C-T is Benign according to our data. Variant chr9-114330016-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2591802.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000608.4. 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
	ORM2	NM_000608.4	MANE Select	c.112C>T	p.Arg38Trp	missense splice_region	Exon 1 of 6	NP_000599.1	P19652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ORM2	ENST00000431067.4	TSL:1 MANE Select	c.112C>T	p.Arg38Trp	missense splice_region	Exon 1 of 6	ENSP00000394936.2	P19652
ORM2	ENST00000893195.1		c.112C>T	p.Arg38Trp	missense splice_region	Exon 1 of 7	ENSP00000563254.1
ORM2	ENST00000893198.1		c.112C>T	p.Arg38Trp	missense splice_region	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes

AF:

0.000130

AC:

AN:

145756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000867

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000593

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

212394

AF XY:

0.000139

show subpopulations

Gnomad AFR exome

AF:

0.000402

Gnomad AMR exome

AF:

0.0000658

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000317

Gnomad OTH exome

AF:

0.000370

GnomAD4 exome

AF:

0.0000718

AC:

103

AN:

1434822

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

712162

show subpopulations

African (AFR)

AF:

0.000160

AC:

AN:

31206

American (AMR)

AF:

0.000146

AC:

AN:

41054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25708

East Asian (EAS)

AF:

0.00

AC:

AN:

38736

South Asian (SAS)

AF:

0.000612

AC:

AN:

83384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51952

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

1097790

Other (OTH)

AF:

0.000152

AC:

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000130

AC:

AN:

145848

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

71126

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

36840

American (AMR)

AF:

0.00

AC:

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5022

South Asian (SAS)

AF:

0.000868

AC:

AN:

4606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000593

AC:

AN:

67432

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000465

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000133

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.70

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

PhyloP100

-1.1

PROVEAN

Benign

1.8

REVEL

Benign

0.021

Sift

Benign

0.28

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.14

MVP

0.12

MPC

2.3

ClinPred

0.020

GERP RS

-5.3

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.17

gMVP

0.57

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.050

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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