Variant 9-114323246-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000607.4(ORM1):c.113G>A(p.Arg38Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,560,514 control chromosomes in the GnomAD database, including 280,784 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 23687 hom., cov: 24)

Exomes 𝑓: 0.61 ( 257097 hom. )

Consequence

ORM1
NM_000607.4 missense, splice_region

Scores

Splicing: ADA: 0.00001714

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.177975E-5).

BP6

Variant 9-114323246-G-A is Benign according to our data. Variant chr9-114323246-G-A is described in ClinVar as [Benign]. Clinvar id is 768319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM1	NM_000607.4 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant, splice_region_variant	1/6	ENST00000259396.9	NP_000598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM1	ENST00000259396.9 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant, splice_region_variant	1/6	1	NM_000607.4	ENSP00000259396	P1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

84507

AN:

141686

Hom.:

23671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.532

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.601

GnomAD3 exomes

AF:

0.633

AC:

136872

AN:

216240

Hom.:

42398

AF XY:

0.635

AC XY:

74181

AN XY:

116856

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.653

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.606

AC:

859570

AN:

1418724

Hom.:

257097

Cov.:

AF XY:

0.607

AC XY:

427915

AN XY:

704482

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.687

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.596

AC:

84564

AN:

141790

Hom.:

23687

Cov.:

AF XY:

0.601

AC XY:

41420

AN XY:

68880

show subpopulations

Gnomad4 AFR

AF:

0.532

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.636

Gnomad4 FIN

AF:

0.686

Gnomad4 NFE

AF:

0.599

Gnomad4 OTH

AF:

0.604

Alfa

AF:

0.535

Hom.:

2377

ExAC

AF:

0.602

AC:

72162

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.038

DANN

Benign

0.68

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0085

MetaRNN

Benign

0.000082

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.17

PROVEAN

Benign

0.49

REVEL

Benign

0.0020

Sift

Benign

0.53

Sift4G

Benign

0.43

Vest4

0.027

MPC

1.8

ClinPred

0.0041

GERP RS

-7.6

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.046

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