Variant rs11556087 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_058164.4(OLFM2):c.380C>T(p.Thr127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,302 control chromosomes in the GnomAD database, including 36,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2369 hom., cov: 32)

Exomes 𝑓: 0.20 ( 33639 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OLFM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, OLFM2

BP4

Computational evidence support a benign effect (MetaRNN=0.0019342303).

BP6

Variant 19-9857463-G-A is Benign according to our data. Variant chr19-9857463-G-A is described in ClinVar as [Benign]. Clinvar id is 1245907.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFM2	NM_058164.4 linkuse as main transcript	c.380C>T	p.Thr127Met	missense_variant	4/6	ENST00000264833.9
OLFM2	NM_001304347.2 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	4/6
OLFM2	NM_001304348.2 linkuse as main transcript	c.146C>T	p.Thr49Met	missense_variant	3/5
OLFM2	XM_047439713.1 linkuse as main transcript	c.176C>T	p.Thr59Met	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFM2	ENST00000264833.9 linkuse as main transcript	c.380C>T	p.Thr127Met	missense_variant	4/6	1	NM_058164.4

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22876

AN:

152046

Hom.:

2371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.153

AC:

38377

AN:

250354

Hom.:

4068

AF XY:

0.154

AC XY:

20857

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0416

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.202

AC:

295778

AN:

1461138

Hom.:

33639

Cov.:

AF XY:

0.199

AC XY:

144379

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.0356

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0434

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.150

AC:

22858

AN:

152164

Hom.:

2369

Cov.:

AF XY:

0.142

AC XY:

10589

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0417

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.215

Hom.:

5772

Bravo

AF:

0.145

TwinsUK

AF:

0.235

AC:

872

ALSPAC

AF:

0.244

AC:

942

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.242

AC:

2079

ExAC

AF:

0.151

AC:

18288

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.239

EpiControl

AF:

0.236

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.86

D;D;D

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;.;.

REVEL

Benign

0.24

Sift

Uncertain

0.015

D;.;.

Sift4G

Uncertain

0.020

D;T;.

Polyphen

0.99

D;.;.

Vest4

0.10

MPC

1.3

ClinPred

0.013

GERP RS

4.0

Varity_R

0.035

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over