rs756430892

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015441.3(OLFML2B):​c.1580G>T​(p.Arg527Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R527Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

4
12
3

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OLFML2BNM_015441.3 linkc.1580G>T p.Arg527Leu missense_variant Exon 7 of 8 ENST00000294794.8 NP_056256.1 Q68BL8-1
OLFML2BNM_001347700.2 linkc.1586G>T p.Arg529Leu missense_variant Exon 7 of 8 NP_001334629.1
OLFML2BNM_001297713.2 linkc.1583G>T p.Arg528Leu missense_variant Exon 7 of 8 NP_001284642.1 Q68BL8F2Z3N3B4DWE8
OLFML2BXM_011509398.3 linkc.860G>T p.Arg287Leu missense_variant Exon 4 of 5 XP_011507700.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OLFML2BENST00000294794.8 linkc.1580G>T p.Arg527Leu missense_variant Exon 7 of 8 1 NM_015441.3 ENSP00000294794.3 Q68BL8-1
OLFML2BENST00000367940.2 linkc.1583G>T p.Arg528Leu missense_variant Exon 7 of 8 2 ENSP00000356917.2 F2Z3N3
OLFML2BENST00000367938.1 linkc.29G>T p.Arg10Leu missense_variant Exon 1 of 2 2 ENSP00000356915.1 Q68BL8-2

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251462
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
27
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T;D;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.70
D;D;D
MetaSVM
Uncertain
0.38
D
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-4.7
D;D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.014
D;D;D
Polyphen
0.79
P;P;.
Vest4
0.82
MutPred
0.44
.;Loss of ubiquitination at K525 (P = 0.0433);.;
MVP
0.91
MPC
0.59
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.41
gMVP
0.78

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.

Other links and lift over

dbSNP: rs756430892; hg19: chr1-161954665; API