rs2233549

chr11-77103064-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006189.1(OMP):c.225G>A(p.Pro75=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMP	NM_006189.1	c.225G>A	p.Pro75=	synonymous_variant	1/1	ENST00000529803.1
CAPN5	NM_004055.5	c.297+9251G>A		intron_variant		ENST00000648180.1
CAPN5	XM_011545225.1	c.417+9251G>A		intron_variant
CAPN5	XM_017018223.3	c.405+9251G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMP	ENST00000529803.1	c.225G>A	p.Pro75=	synonymous_variant	1/1		NM_006189.1	P1
CAPN5	ENST00000648180.1	c.297+9251G>A		intron_variant			NM_004055.5	P1

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

GnomAD3 exomes AF: 0.218 AC: 54044 AN: 248082 Hom.: 6139 AF XY: 0.222 AC XY: 29983 AN XY: 134788

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 SAS exome AF: 0.308

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

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.217

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

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.212

Alfa AF: 0.202 Hom.: 6514

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.2
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233549; hg19: chr11-76814110; COSMIC: COSV53686324;