Variant chr9-114331643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000608.4(ORM2):c.405C>T(p.Asp135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,613,856 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 41 hom. )

Consequence

ORM2
NM_000608.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.30

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:

AKNA (HGNC:):

AKNA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-114331643-C-T is Benign according to our data. Variant chr9-114331643-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659443.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.3 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM2	NM_000608.4 linkuse as main transcript	c.405C>T	p.Asp135=	synonymous_variant	4/6	ENST00000431067.4	NP_000599.1
AKNA	XR_929844.4 linkuse as main transcript	n.8318G>A		non_coding_transcript_exon_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4 linkuse as main transcript	c.405C>T	p.Asp135=	synonymous_variant	4/6	1	NM_000608.4	ENSP00000394936	P1

Frequencies

GnomAD3 genomes

AF:

0.00444

AC:

675

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00433

AC:

1088

AN:

251464

Hom.:

AF XY:

0.00430

AC XY:

585

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.0316

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.00345

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00317

AC:

4630

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

2278

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.00478

Gnomad4 ASJ exome

AF:

0.0316

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00246

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.00443

AC:

674

AN:

152112

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00478

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00518

Hom.:

Bravo

AF:

0.00505

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00498

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: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.095

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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