chr1-161983763-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015441.3(OLFML2B):​c.2165C>A​(p.Thr722Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,922 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OLFML2B
NM_015441.3 missense

Scores

8
9
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.86
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OLFML2BNM_015441.3 linkuse as main transcriptc.2165C>A p.Thr722Asn missense_variant 8/8 ENST00000294794.8
OLFML2BNM_001347700.2 linkuse as main transcriptc.2171C>A p.Thr724Asn missense_variant 8/8
OLFML2BNM_001297713.2 linkuse as main transcriptc.2168C>A p.Thr723Asn missense_variant 8/8
OLFML2BXM_011509398.3 linkuse as main transcriptc.1445C>A p.Thr482Asn missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OLFML2BENST00000294794.8 linkuse as main transcriptc.2165C>A p.Thr722Asn missense_variant 8/81 NM_015441.3 P3Q68BL8-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251494
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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
AF:
0.0000132
AC:
2
AN:
152028
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;D;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.4
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Pathogenic
0.68
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0020
D;D;T
Polyphen
1.0
D;D;.
Vest4
0.91
MutPred
0.50
.;Loss of phosphorylation at T723 (P = 0.0334);.;
MVP
0.93
MPC
0.60
ClinPred
0.97
D
GERP RS
5.6
Varity_R
0.67
gMVP
0.79

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: rs1482872581; hg19: chr1-161953553; API