chr1-161984867-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015441.3(OLFML2B):​c.1588G>T​(p.Val530Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

OLFML2B
NM_015441.3 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OLFML2BNM_015441.3 linkuse as main transcriptc.1588G>T p.Val530Leu missense_variant 7/8 ENST00000294794.8
OLFML2BNM_001347700.2 linkuse as main transcriptc.1594G>T p.Val532Leu missense_variant 7/8
OLFML2BNM_001297713.2 linkuse as main transcriptc.1591G>T p.Val531Leu missense_variant 7/8
OLFML2BXM_011509398.3 linkuse as main transcriptc.868G>T p.Val290Leu missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML2BENST00000294794.8 linkuse as main transcriptc.1588G>T p.Val530Leu missense_variant 7/81 NM_015441.3 P3Q68BL8-1
OLFML2BENST00000367940.2 linkuse as main transcriptc.1591G>T p.Val531Leu missense_variant 7/82 A2
OLFML2BENST00000367938.1 linkuse as main transcriptc.37G>T p.Val13Leu missense_variant 1/22 Q68BL8-2

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727228
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

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.1588G>T (p.V530L) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a G to T substitution at nucleotide position 1588, causing the valine (V) at amino acid position 530 to be replaced by a leucine (L). 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
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.30
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;D;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.77
D;D;D
MetaSVM
Uncertain
0.77
D
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.3
N;N;N
REVEL
Pathogenic
0.80
Sift
Benign
0.059
T;T;T
Sift4G
Uncertain
0.0090
D;D;T
Polyphen
0.75
P;P;.
Vest4
0.82
MutPred
0.61
.;Gain of catalytic residue at V531 (P = 0.0722);.;
MVP
0.89
MPC
0.45
ClinPred
0.93
D
GERP RS
4.3
Varity_R
0.26
gMVP
0.72

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: rs749921063; hg19: chr1-161954657; API