rs17650

chr9-114323246-G-Achr9-114323246-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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, single submitter B:1
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ORM1	NM_000607.4	c.113G>A	p.Arg38Gln	missense_variant, splice_region_variant	1/6	ENST00000259396.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.596 AC: 84507 AN: 141686 Hom.: 23671 Cov.: 24

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

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.: 34 AF XY: 0.607 AC XY: 427915 AN XY: 704482

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.: 24 AF XY: 0.601 AC XY: 41420 AN XY: 68880

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.86	T
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	N
MetaRNN	Benign	0.000082	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.0020
Sift	Benign	0.53	T
Sift4G	Benign	0.43	T
Vest4		0.027
MPC		1.8
ClinPred		0.0041	T
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

Other links and lift over

dbSNP: rs17650; hg19: chr9-117085526; COSMIC: COSV52277829; COSMIC: COSV52277829;