Genetic Variant ORM2:p.Glu17Lys (chr9-114329953-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000608.4(ORM2):c.49G>A(p.Glu17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ORM2
NM_000608.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0370

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013358176).

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.49G>A	p.Glu17Lys	missense	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.49G>A	p.Glu17Lys	missense	Exon 1 of 6	ENSP00000394936.2	P19652
ORM2	ENST00000893195.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 7	ENSP00000563254.1
ORM2	ENST00000893198.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

118364

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000154

AC:

AN:

208006

AF XY:

0.000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000663

Gnomad ASJ exome

AF:

0.00116

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.000390

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000320

AC:

AN:

1407242

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

694544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29596

American (AMR)

AF:

0.000595

AC:

AN:

40318

Ashkenazi Jewish (ASJ)

AF:

0.000572

AC:

AN:

24458

East Asian (EAS)

AF:

0.00

AC:

AN:

38788

South Asian (SAS)

AF:

0.00

AC:

AN:

83116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4670

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1076058

Other (OTH)

AF:

0.0000866

AC:

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

118364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56074

African (AFR)

AF:

0.00

AC:

AN:

24390

American (AMR)

AF:

0.00

AC:

AN:

11938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3186

East Asian (EAS)

AF:

0.00

AC:

AN:

4142

South Asian (SAS)

AF:

0.00

AC:

AN:

3364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61004

Other (OTH)

AF:

0.00

AC:

AN:

1566

Alfa

AF:

0.0000959

Hom.:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.24

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.011

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.78

M_CAP

Benign

0.0031

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.037

PROVEAN

Benign

-1.9

REVEL

Benign

0.023

Sift

Benign

0.28

Sift4G

Benign

0.14

Polyphen

0.28

Vest4

0.20

MutPred

0.43

Gain of ubiquitination at E17 (P = 0.0198)

MVP

0.18

MPC

2.0

ClinPred

0.015

GERP RS

-2.8

PromoterAI

-0.0020

Neutral

(source)

Varity_R

0.11

gMVP

0.42

Mutation Taster

=90/10

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over