9-114325784-T-A

Variant names:

• chr9-114325784-T-A
• rs10982156
• NM_000607.4:c.541-508T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000607.4(ORM1):​c.541-508T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 151,362 control chromosomes in the GnomAD database, including 27 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 0.070 (27 hom., cov: 33)
• Consequence: ORM1 NM_000607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• Publications: 13 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM1	NM_000607.4	MANE Select	c.541-508T>A		intron	N/A	NP_000598.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM1	ENST00000259396.9	TSL:1 MANE Select	c.541-508T>A		intron	N/A	ENSP00000259396.8

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10560 AN: 151242 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0808

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0697 AC: 10556 AN: 151362 Hom.: 27 Cov.: 33 AF XY: 0.0684 AC XY: 5067 AN XY: 74034

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0756 AC: 3118 AN: 41218

American (AMR) AF: 0.0823 AC: 1252 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 201 AN: 3454

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5176

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4818

European-Finnish (FIN) AF: 0.0324 AC: 343 AN: 10594

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0721 AC: 4876 AN: 67586

Other (OTH) AF: 0.0800 AC: 168 AN: 2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0706 Hom.: 0

Asia WGS AF: 0.0500 AC: 172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.47
PhyloP100		-0.55
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: rs10982156; hg19: chr9-117088064;