rs17650

Variant names:

• chr9-114323246-G-A
• rs17650
• NM_000607.4:c.113G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-114323246-G-A
• chr9-114323246-G-C
• chr9-114323246-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 16/21 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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ORM1	NM_000607.4	c.113G>A	p.Arg38Gln	missense_variant, splice_region_variant	Exon 1 of 6	ENST00000259396.9	NP_000598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORM1	ENST00000259396.9	c.113G>A	p.Arg38Gln	missense_variant, splice_region_variant	Exon 1 of 6	1	NM_000607.4	ENSP00000259396.8

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

GnomAD2 exomes AF: 0.633 AC: 136872 AN: 216240 AF XY: 0.635

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 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

African (AFR) AF: 0.507 AC: 15791 AN: 31152

American (AMR) AF: 0.645 AC: 25893 AN: 40132

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 14966 AN: 25424

East Asian (EAS) AF: 0.751 AC: 28034 AN: 37310

South Asian (SAS) AF: 0.652 AC: 53771 AN: 82426

European-Finnish (FIN) AF: 0.687 AC: 35263 AN: 51294

Middle Eastern (MID) AF: 0.607 AC: 3414 AN: 5622

European-Non Finnish (NFE) AF: 0.595 AC: 646660 AN: 1086958

Other (OTH) AF: 0.613 AC: 35778 AN: 58406

GnomAD4 genome AF: 0.596 AC: 84564 AN: 141790 Hom.: 23687 Cov.: 24 AF XY: 0.601 AC XY: 41420 AN XY: 68880

African (AFR) AF: 0.532 AC: 19472 AN: 36588

American (AMR) AF: 0.623 AC: 8889 AN: 14262

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2003 AN: 3366

East Asian (EAS) AF: 0.741 AC: 3402 AN: 4592

South Asian (SAS) AF: 0.636 AC: 2756 AN: 4332

European-Finnish (FIN) AF: 0.686 AC: 6799 AN: 9906

Middle Eastern (MID) AF: 0.575 AC: 161 AN: 280

European-Non Finnish (NFE) AF: 0.599 AC: 39318 AN: 65646

Other (OTH) AF: 0.604 AC: 1168 AN: 1934

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

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		-1.4
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
PromoterAI		0.069	Neutral
gMVP		0.32
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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