chr17-47809159-C-T

Variant summary

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

The NM_145798.3(OSBPL7):​c.2087G>A​(p.Arg696His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,028 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

OSBPL7
NM_145798.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.704
Variant links:
Genes affected
OSBPL7 (HGNC:16387): (oxysterol binding protein like 7) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Two transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

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=0.2691759).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSBPL7NM_145798.3 linkc.2087G>A p.Arg696His missense_variant 20/23 ENST00000007414.8 NP_665741.1 Q9BZF2-1Q8WXP9
OSBPL7XM_047435292.1 linkc.2087G>A p.Arg696His missense_variant 20/23 XP_047291248.1
OSBPL7XM_047435293.1 linkc.2033G>A p.Arg678His missense_variant 19/22 XP_047291249.1
OSBPL7XR_934362.2 linkn.2303G>A non_coding_transcript_exon_variant 20/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSBPL7ENST00000007414.8 linkc.2087G>A p.Arg696His missense_variant 20/231 NM_145798.3 ENSP00000007414.3 Q9BZF2-1
OSBPL7ENST00000613735.4 linkn.*246-44G>A intron_variant 1 ENSP00000479827.1 Q9BZF2-2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251250
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135846
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:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000479
AC:
70
AN:
1461848
Hom.:
0
Cov.:
34
AF XY:
0.0000550
AC XY:
40
AN XY:
727226
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000603
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000989
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 GeneticsDec 02, 2022The c.2087G>A (p.R696H) alteration is located in exon 20 (coding exon 19) of the OSBPL7 gene. This alteration results from a G to A substitution at nucleotide position 2087, causing the arginine (R) at amino acid position 696 to be replaced by a histidine (H). 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
0.084
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.40
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.065
T;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.23
N
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.8
L;L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.26
MVP
0.66
MPC
1.2
ClinPred
0.44
T
GERP RS
5.0
Varity_R
0.14

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: rs376859496; hg19: chr17-45886525; COSMIC: COSV50109878; COSMIC: COSV50109878; API