Variant 9-114325132-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_000607.4(ORM1):c.520G>A(p.Val174Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,603,804 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.028 ( 46 hom., cov: 33)

Exomes 𝑓: 0.022 ( 437 hom. )

Consequence

ORM1
NM_000607.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032133162).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0281 (4206/149920) while in subpopulation AFR AF= 0.0464 (1844/39756). AF 95% confidence interval is 0.0446. There are 46 homozygotes in gnomad4. There are 2025 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM1	NM_000607.4 linkuse as main transcript	c.520G>A	p.Val174Met	missense_variant	5/6	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.520G>A	p.Val174Met	missense_variant	5/6	1	NM_000607.4	ENSP00000259396.8		P02763
ORM1	ENST00000477456.1 linkuse as main transcript	n.303G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4210

AN:

149808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0102

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00707

Gnomad FIN

AF:

0.0268

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.0241

GnomAD3 exomes

AF:

0.0193

AC:

4813

AN:

250014

Hom.:

AF XY:

0.0185

AC XY:

2501

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.00969

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00453

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0254

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0224

AC:

32603

AN:

1453884

Hom.:

437

Cov.:

AF XY:

0.0215

AC XY:

15575

AN XY:

723296

show subpopulations

Gnomad4 AFR exome

AF:

0.0426

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00522

Gnomad4 FIN exome

AF:

0.0304

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0281

AC:

4206

AN:

149920

Hom.:

Cov.:

AF XY:

0.0276

AC XY:

2025

AN XY:

73304

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0102

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00687

Gnomad4 FIN

AF:

0.0268

Gnomad4 NFE

AF:

0.0249

Gnomad4 OTH

AF:

0.0239

Alfa

AF:

0.0216

Hom.:

Bravo

AF:

0.0285

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.0415

AC:

183

ESP6500EA

AF:

0.0222

AC:

191

ExAC

AF:

0.0222

AC:

2693

EpiCase

AF:

0.0214

EpiControl

AF:

0.0218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.16

DANN

Benign

0.72

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0012

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.16

REVEL

Benign

0.030

Sift

Benign

0.63

Sift4G

Benign

0.42

Vest4

0.026

MPC

0.040

ClinPred

0.0043

GERP RS

-8.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over