11-77102915-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006189.1(OMP):c.76C>T(p.Arg26Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,612,714 control chromosomes in the GnomAD database, including 3,369 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R26Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.053 ( 409 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2960 hom. )

Consequence

OMP
NM_006189.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025221407).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OMP	NM_006189.1 link	c.76C>T	p.Arg26Trp	missense_variant	Exon 1 of 1	ENST00000529803.1	NP_006180.1	P47874
CAPN5	NM_004055.5 link	c.297+9102C>T		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.76C>T	p.Arg26Trp	missense_variant	Exon 1 of 1	6	NM_006189.1	ENSP00000436376.1		P47874
CAPN5	ENST00000648180.1 link	c.297+9102C>T		intron_variant	Intron 3 of 12		NM_004055.5	ENSP00000498132.1		O15484

Frequencies

GnomAD3 genomes

AF:

0.0528

AC:

8038

AN:

152234

Hom.:

410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0573

GnomAD2 exomes

AF:

0.0699

AC:

17180

AN:

245804

AF XY:

0.0623

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.0321

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0551

Gnomad OTH exome

AF:

0.0668

GnomAD4 exome

AF:

0.0553

AC:

80789

AN:

1460362

Hom.:

2960

Cov.:

AF XY:

0.0533

AC XY:

38707

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.00911

AC:

305

AN:

33478

American (AMR)

AF:

0.203

AC:

9068

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0322

AC:

841

AN:

26126

East Asian (EAS)

AF:

0.000453

AC:

AN:

39698

South Asian (SAS)

AF:

0.0208

AC:

1797

AN:

86248

European-Finnish (FIN)

AF:

0.114

AC:

5978

AN:

52244

Middle Eastern (MID)

AF:

0.0193

AC:

110

AN:

5700

European-Non Finnish (NFE)

AF:

0.0537

AC:

59721

AN:

1111822

Other (OTH)

AF:

0.0489

AC:

2951

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4631

9263

13894

18526

23157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2246

4492

6738

8984

11230

<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:

0.0528

AC:

8045

AN:

152352

Hom.:

409

Cov.:

AF XY:

0.0559

AC XY:

4166

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0112

AC:

464

AN:

41588

American (AMR)

AF:

0.153

AC:

2335

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0205

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.110

AC:

1168

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3682

AN:

68022

Other (OTH)

AF:

0.0562

AC:

119

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

362

725

1087

1450

1812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0476

Hom.:

219

Bravo

AF:

0.0554

TwinsUK

AF:

0.0518

AC:

192

ALSPAC

AF:

0.0547

AC:

211

ESP6500AA

AF:

0.0130

AC:

ESP6500EA

AF:

0.0527

AC:

443

ExAC

AF:

0.0617

AC:

7465

EpiCase

AF:

0.0491

EpiControl

AF:

0.0487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.4

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.24

Sift

Benign

0.033

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.93

MPC

0.14

ClinPred

0.036

GERP RS

1.9

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.51

gMVP

0.46

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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