Variant chr1-161984875-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015441.3(OLFML2B):c.1580G>A(p.Arg527Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 3.21

Variant links:

Genes affected

OLFML2B (HGNC:24558): (olfactomedin like 2B) This gene encodes an olfactomedin domain-containing protein. Most olfactomedin domain-containing proteins are secreted glycoproteins. [provided by RefSeq, Dec 2016]

OLFML2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30183753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLFML2B	NM_015441.3 linkuse as main transcript	c.1580G>A	p.Arg527Gln	missense_variant	7/8	ENST00000294794.8
OLFML2B	NM_001347700.2 linkuse as main transcript	c.1586G>A	p.Arg529Gln	missense_variant	7/8
OLFML2B	NM_001297713.2 linkuse as main transcript	c.1583G>A	p.Arg528Gln	missense_variant	7/8
OLFML2B	XM_011509398.3 linkuse as main transcript	c.860G>A	p.Arg287Gln	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8 linkuse as main transcript	c.1580G>A	p.Arg527Gln	missense_variant	7/8	1	NM_015441.3	P3	Q68BL8-1
OLFML2B	ENST00000367940.2 linkuse as main transcript	c.1583G>A	p.Arg528Gln	missense_variant	7/8	2		A2
OLFML2B	ENST00000367938.1 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/2	2			Q68BL8-2

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251462

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150540

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73300

show subpopulations

Gnomad4 AFR

AF:

0.000147

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000486

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Medizinische Klinik 1/ Institut für Bioinformatik, Universitätsklinikum Großhadern, München/ Helmholtz Zentrum München

Aug 01, 2015

- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.1580G>A (p.R527Q) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a G to A substitution at nucleotide position 1580, causing the arginine (R) at amino acid position 527 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.46

T;D;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.97

D;D;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;N;N

REVEL

Uncertain

0.56

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.59

P;P;.

Vest4

0.52

MutPred

0.43

.;Gain of catalytic residue at R528 (P = 0.0888);.;

MVP

0.84

MPC

0.38

ClinPred

0.26

GERP RS

4.3

Varity_R

0.27

gMVP

0.68

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