9-114330749-C-T

Position:

• chr9-114330749-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000608.4(ORM2):​c.258-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,604,962 control chromosomes in the GnomAD database, including 33,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2361 hom., cov: 31)
  • Exomes 𝑓: 0.20 (31161 hom.)
• Consequence: ORM2 NM_000608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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]

AKNA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM2	NM_000608.4	c.258-43C>T		intron_variant		ENST00000431067.4	NP_000599.1
AKNA	XR_929844.4	n.9212G>A		non_coding_transcript_exon_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4	c.258-43C>T		intron_variant		1	NM_000608.4	ENSP00000394936	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25277 AN: 151834 Hom.: 2361 Cov.: 31

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.186 AC: 46644 AN: 250622 Hom.: 4927 AF XY: 0.194 AC XY: 26349 AN XY: 135486

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.282

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.201 AC: 292763 AN: 1453012 Hom.: 31161 Cov.: 29 AF XY: 0.204 AC XY: 147809 AN XY: 723430

Gnomad4 AFR exome AF: 0.0923

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.166 AC: 25290 AN: 151950 Hom.: 2361 Cov.: 31 AF XY: 0.167 AC XY: 12426 AN XY: 74290

Gnomad4 AFR AF: 0.0963

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.184

Alfa AF: 0.187 Hom.: 5503

Bravo AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs17230081; hg19: chr9-117093029; COSMIC: COSV52278795; COSMIC: COSV52278795;