Genetic Variant OMP:p.Pro75Pro (chr11-77103064-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.47

Publications

13 publications found

Variant links:

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]

OMP links:

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

CAPN5 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OMP	NM_006189.1 link	c.225G>A	p.Pro75Pro	synonymous_variant	Exon 1 of 1	ENST00000529803.1	NP_006180.1	P47874
CAPN5	NM_004055.5 link	c.297+9251G>A		intron_variant	Intron 3 of 12	ENST00000648180.1	NP_004046.2	O15484A0A140VKH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMP	ENST00000529803.1 link	c.225G>A	p.Pro75Pro	synonymous_variant	Exon 1 of 1	6	NM_006189.1	ENSP00000436376.1		P47874
CAPN5	ENST00000648180.1 link	c.297+9251G>A		intron_variant	Intron 3 of 12		NM_004055.5	ENSP00000498132.1		O15484

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31523

AN:

152058

Hom.:

3409

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.213

AC XY:

154799

AN XY:

726926

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16801

33603

50404

67206

84007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8020

16040

24060

32080

40100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31556

AN:

152178

Hom.:

3416

Cov.:

AF XY:

0.211

AC XY:

15673

AN XY:

74380

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13665

AN:

67982

Other (OTH)

AF:

0.212

AC:

447

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1317

2635

3952

5270

6587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.2

(source)

DANN

Benign

0.87

PhyloP100

-6.5

PromoterAI

-0.0046

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over