NM_000608.4:c.258-43C>T

Variant names:

• chr9-114330749-C-T
• rs17230081
• NM_000608.4:c.258-43C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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]

AKNA (HGNC:24108): (AT-hook transcription factor) Predicted to enable DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in centrosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ORM2	NM_000608.4	c.258-43C>T		intron_variant	Intron 2 of 5	ENST00000431067.4	NP_000599.1
AKNA	XR_929844.4	n.9212G>A		non_coding_transcript_exon_variant	Exon 23 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4	c.258-43C>T		intron_variant	Intron 2 of 5	1	NM_000608.4	ENSP00000394936.2

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

GnomAD2 exomes AF: 0.186 AC: 46644 AN: 250622 AF XY: 0.194

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 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

African (AFR) AF: 0.0923 AC: 3052 AN: 33076

American (AMR) AF: 0.139 AC: 6230 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3878 AN: 26036

East Asian (EAS) AF: 0.193 AC: 7660 AN: 39640

South Asian (SAS) AF: 0.282 AC: 24294 AN: 86096

European-Finnish (FIN) AF: 0.141 AC: 7546 AN: 53390

Middle Eastern (MID) AF: 0.190 AC: 1089 AN: 5746

European-Non Finnish (NFE) AF: 0.205 AC: 226857 AN: 1104300

Other (OTH) AF: 0.202 AC: 12157 AN: 60058

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

African (AFR) AF: 0.0963 AC: 3984 AN: 41364

American (AMR) AF: 0.171 AC: 2616 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1072 AN: 5144

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4812

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10588

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13651 AN: 67982

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.183 Hom.: 8172

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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