chr9-114329923-C-T

Variant names:

• chr9-114329923-C-T
• rs143336597
• NM_000608.4:c.19C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000608.4(ORM2):​c.19C>T​(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,449,352 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0030 (32 hom.)
• Consequence: ORM2 NM_000608.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.953
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045836866).
• BP6: Variant 9-114329923-C-T is Benign according to our data. Variant chr9-114329923-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM2	NM_000608.4	MANE Select	c.19C>T	p.Leu7Phe	missense	Exon 1 of 6	NP_000599.1	P19652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM2	ENST00000431067.4	TSL:1 MANE Select	c.19C>T	p.Leu7Phe	missense	Exon 1 of 6	ENSP00000394936.2	P19652
	ORM2	ENST00000893195.1		c.19C>T	p.Leu7Phe	missense	Exon 1 of 7	ENSP00000563254.1
	ORM2	ENST00000893198.1		c.19C>T	p.Leu7Phe	missense	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 457 AN: 109512 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.00465

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00467

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.000265

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00270

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00801

GnomAD2 exomes AF: 0.00398 AC: 630 AN: 158422 AF XY: 0.00394

Gnomad AFR exome AF: 0.00493

Gnomad AMR exome AF: 0.00479

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.0000703

Gnomad FIN exome AF: 0.00314

Gnomad NFE exome AF: 0.00340

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00303 AC: 4066 AN: 1339762 Hom.: 32 Cov.: 23 AF XY: 0.00299 AC XY: 1967 AN XY: 658672

African (AFR) AF: 0.00586 AC: 158 AN: 26946

American (AMR) AF: 0.00486 AC: 163 AN: 33526

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 671 AN: 21518

East Asian (EAS) AF: 0.00 AC: 0 AN: 38080

South Asian (SAS) AF: 0.00138 AC: 104 AN: 75116

European-Finnish (FIN) AF: 0.00192 AC: 97 AN: 50554

Middle Eastern (MID) AF: 0.0100 AC: 39 AN: 3898

European-Non Finnish (NFE) AF: 0.00242 AC: 2509 AN: 1035148

Other (OTH) AF: 0.00591 AC: 325 AN: 54976

GnomAD4 genome AF: 0.00416 AC: 456 AN: 109590 Hom.: 0 Cov.: 14 AF XY: 0.00425 AC XY: 218 AN XY: 51260

African (AFR) AF: 0.00464 AC: 106 AN: 22844

American (AMR) AF: 0.00456 AC: 49 AN: 10736

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 89 AN: 3046

East Asian (EAS) AF: 0.000266 AC: 1 AN: 3762

South Asian (SAS) AF: 0.00108 AC: 3 AN: 2768

European-Finnish (FIN) AF: 0.00270 AC: 18 AN: 6672

Middle Eastern (MID) AF: 0.0207 AC: 5 AN: 242

European-Non Finnish (NFE) AF: 0.00303 AC: 174 AN: 57334

Other (OTH) AF: 0.00788 AC: 11 AN: 1396

Alfa AF: 0.00560 Hom.: 5

Bravo AF: 0.00483

ESP6500AA AF: 0.00260 AC: 11

ESP6500EA AF: 0.00551 AC: 47

ExAC AF: 0.00312 AC: 373

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.95
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.054
Sift	Benign	0.10	T
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.33
MVP		0.32
MPC		1.6
ClinPred		0.036	T
GERP RS		1.9
PromoterAI		-0.0074	Neutral
Varity_R		0.10
gMVP		0.31
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143336597; hg19: chr9-117092203;