Variant 9-114329923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000608.4(ORM2):c.19C>T(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,449,352 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0030 ( 32 hom. )

Consequence

ORM2
NM_000608.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.953

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045836866).

BP6

Variant 9-114329923-C-T is Benign according to our data. Variant chr9-114329923-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659442.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM2	NM_000608.4 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/6	ENST00000431067.4	NP_000599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/6	1	NM_000608.4	ENSP00000394936	P1

Frequencies

GnomAD3 genomes

AF:

0.00417

AC:

457

AN:

109512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00465

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00467

Gnomad ASJ

AF:

0.0292

Gnomad EAS

AF:

0.000265

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.00270

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00801

GnomAD3 exomes

AF:

0.00398

AC:

630

AN:

158422

Hom.:

AF XY:

0.00394

AC XY:

333

AN XY:

84618

show subpopulations

Gnomad AFR exome

AF:

0.00493

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.0000703

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00303

AC:

4066

AN:

1339762

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

1967

AN XY:

658672

show subpopulations

Gnomad4 AFR exome

AF:

0.00586

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00192

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00591

GnomAD4 genome

AF:

0.00416

AC:

456

AN:

109590

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

218

AN XY:

51260

show subpopulations

Gnomad4 AFR

AF:

0.00464

Gnomad4 AMR

AF:

0.00456

Gnomad4 ASJ

AF:

0.0292

Gnomad4 EAS

AF:

0.000266

Gnomad4 SAS

AF:

0.00108

Gnomad4 FIN

AF:

0.00270

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.00788

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.00483

ESP6500AA

AF:

0.00260

AC:

ESP6500EA

AF:

0.00551

AC:

ExAC

AF:

0.00312

AC:

373

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ORM2: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.090

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.054

Sift

Benign

0.10

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.33

MVP

0.32

MPC

1.6

ClinPred

0.036

GERP RS

1.9

Varity_R

0.10

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over