Variant 9-114324076-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000607.4(ORM1):c.316A>G(p.Ile106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,613,876 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 2 hom. )

Consequence

ORM1
NM_000607.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -7.96

Variant links:

Genes affected

ORM1 (HGNC:8498): (orosomucoid 1) 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]

ORM1 links:

ORM1 (HGNC:):

ORM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014150888).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM1	NM_000607.4 linkuse as main transcript	c.316A>G	p.Ile106Val	missense_variant	3/6	ENST00000259396.9	NP_000598.2	P02763

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM1	ENST00000259396.9 linkuse as main transcript	c.316A>G	p.Ile106Val	missense_variant	3/6	1	NM_000607.4	ENSP00000259396.8		P02763
ORM1	ENST00000477456.1 linkuse as main transcript	n.99A>G		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000350

AC:

AN:

251470

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000571

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000438

AC:

640

AN:

1461662

Hom.:

Cov.:

AF XY:

0.000455

AC XY:

331

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000503

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000289

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.316A>G (p.I106V) alteration is located in exon 3 (coding exon 3) of the ORM1 gene. This alteration results from a A to G substitution at nucleotide position 316, causing the isoleucine (I) at amino acid position 106 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0010

DANN

Benign

0.34

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0086

M_CAP

Benign

0.0015

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.80

REVEL

Benign

0.019

Sift

Benign

0.20

Sift4G

Benign

0.32

Vest4

0.053

MVP

0.048

MPC

0.036

ClinPred

0.016

GERP RS

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

gMVP

0.20

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