NM_006189.1:c.225G>A

Variant names:

• chr11-77103064-G-A
• rs2233549
• NM_006189.1:c.225G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006189.1(OMP):​c.225G>A​(p.Pro75Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,613,472 control chromosomes in the GnomAD database, including 36,614 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 0.21 (3416 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33198 hom.)
• Consequence: OMP NM_006189.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.47
• Publications: 13 publications found

Genes affected

OMP (HGNC:8136): (olfactory marker protein) Olfactory marker protein is uniquely associated with the mature olfactory receptor neurons in many vertebrate species from fish to man. The OMP gene structure and protein sequence are highly conserved between mouse, rat and human. Results of the mouse knockout studies show that OMP-null mice are compromised in their ability to respond to odor stimuli, and that OMP represents a novel modulatory component of the odor detection/signal transduction cascade. [provided by RefSeq, Jul 2008]

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 Gene-Disease associations (from GenCC):

• CAPN5-related vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant neovascular inflammatory vitreoretinopathy

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-6.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006189.1. 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
	OMP	NM_006189.1	MANE Select	c.225G>A	p.Pro75Pro	synonymous	Exon 1 of 1	NP_006180.1
	CAPN5	NM_004055.5	MANE Select	c.297+9251G>A		intron	N/A	NP_004046.2
	CAPN5	NM_001425321.1		c.417+9251G>A		intron	N/A	NP_001412250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMP	ENST00000529803.1	TSL:6 MANE Select	c.225G>A	p.Pro75Pro	synonymous	Exon 1 of 1	ENSP00000436376.1
	CAPN5	ENST00000648180.1	MANE Select	c.297+9251G>A		intron	N/A	ENSP00000498132.1
	CAPN5	ENST00000529629.5	TSL:1	c.297+9251G>A		intron	N/A	ENSP00000432332.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31523 AN: 152058 Hom.: 3409 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.218 AC: 54044 AN: 248082 AF XY: 0.222

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.211 AC: 307650 AN: 1461294 Hom.: 33198 Cov.: 37 AF XY: 0.213 AC XY: 154799 AN XY: 726926

African (AFR) AF: 0.199 AC: 6657 AN: 33480

American (AMR) AF: 0.196 AC: 8746 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4824 AN: 26136

East Asian (EAS) AF: 0.224 AC: 8893 AN: 39694

South Asian (SAS) AF: 0.303 AC: 26093 AN: 86242

European-Finnish (FIN) AF: 0.236 AC: 12525 AN: 53128

Middle Eastern (MID) AF: 0.170 AC: 978 AN: 5768

European-Non Finnish (NFE) AF: 0.203 AC: 225812 AN: 1111804

Other (OTH) AF: 0.217 AC: 13122 AN: 60368

GnomAD4 genome AF: 0.207 AC: 31556 AN: 152178 Hom.: 3416 Cov.: 33 AF XY: 0.211 AC XY: 15673 AN XY: 74380

African (AFR) AF: 0.194 AC: 8058 AN: 41524

American (AMR) AF: 0.213 AC: 3262 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1183 AN: 5174

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2606 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13665 AN: 67982

Other (OTH) AF: 0.212 AC: 447 AN: 2106

Alfa AF: 0.202 Hom.: 13627

Bravo AF: 0.200

Asia WGS AF: 0.281 AC: 977 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.87
PhyloP100		-6.5
PromoterAI		-0.0046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2233549; hg19: chr11-76814110; COSMIC: COSV53686324;