NM_145798.3:c.1352G>A

Variant names:

Variant summary

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

The NM_145798.3(OSBPL7):c.1352G>A(p.Gly451Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,605,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

OSBPL7
NM_145798.3 missense, splice_region

Scores

Splicing: ADA: 0.02645

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.636

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]

OSBPL7 links:

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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
OSBPL7	NM_145798.3 link	c.1352G>A	p.Gly451Glu	missense_variant, splice_region_variant	Exon 15 of 23	ENST00000007414.8	NP_665741.1	Q9BZF2-1Q8WXP9
OSBPL7	XM_047435292.1 link	c.1352G>A	p.Gly451Glu	missense_variant, splice_region_variant	Exon 15 of 23		XP_047291248.1
OSBPL7	XM_047435293.1 link	c.1298G>A	p.Gly433Glu	missense_variant, splice_region_variant	Exon 14 of 22		XP_047291249.1
OSBPL7	XR_934362.2 link	n.1568G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 15 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OSBPL7	ENST00000007414.8 link	c.1352G>A	p.Gly451Glu	missense_variant, splice_region_variant	Exon 15 of 23	1	NM_145798.3	ENSP00000007414.3	Q9BZF2-1
OSBPL7	ENST00000613735.4 link	n.*245+1504G>A		intron_variant	Intron 12 of 15	1		ENSP00000479827.1	Q9BZF2-2
OSBPL7	ENST00000583167.5 link	n.2402G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 11	2
OSBPL7	ENST00000579728.5 link	n.*182-15G>A		intron_variant	Intron 13 of 21	5		ENSP00000463599.1	J3QLK7

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

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:

0.000103

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000688

AC:

AN:

232710

Hom.:

AF XY:

0.0000625

AC XY:

AN XY:

128070

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

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:

0.000106

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000819

AC:

119

AN:

1452836

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

722500

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000113

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:

0.0000955

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

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:

0.000103

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000417

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1352G>A (p.G451E) alteration is located in exon 15 (coding exon 14) of the OSBPL7 gene. This alteration results from a G to A substitution at nucleotide position 1352, causing the glycine (G) at amino acid position 451 to be replaced by a glutamic acid (E). 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

0.073

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.1

DANN

Benign

0.64

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.025

Sift

Benign

0.57

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0

B;B

Vest4

0.27

MutPred

0.36

Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);

MVP

0.47

MPC

0.54

ClinPred

0.015

GERP RS

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.026

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.26

Position offset: 0

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