Variant 18-24303655-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080597.4(OSBPL1A):c.1156G>C(p.Glu386Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

OSBPL1A
NM_080597.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

Variant links:

Genes affected

OSBPL1A (HGNC:16398): (oxysterol binding protein like 1A) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms. [provided by RefSeq, Jul 2008]

OSBPL1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05988553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OSBPL1A	NM_080597.4 linkuse as main transcript	c.1156G>C	p.Glu386Gln	missense_variant	14/28	ENST00000319481.8
OSBPL1A	NM_001242508.1 linkuse as main transcript	c.10G>C	p.Glu4Gln	missense_variant	2/16
OSBPL1A	XM_017025530.2 linkuse as main transcript	c.1210G>C	p.Glu404Gln	missense_variant	14/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBPL1A	ENST00000319481.8 linkuse as main transcript	c.1156G>C	p.Glu386Gln	missense_variant	14/28	1	NM_080597.4	P1	Q9BXW6-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251344

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461038

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000453

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 submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.1156G>C (p.E386Q) alteration is located in exon 14 (coding exon 13) of the OSBPL1A gene. This alteration results from a G to C substitution at nucleotide position 1156, causing the glutamic acid (E) at amino acid position 386 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.55

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.050

Sift

Benign

0.16

T;D

Sift4G

Benign

0.32

T;T

Polyphen

0.28

B;.

Vest4

0.33

MVP

0.55

MPC

0.13

ClinPred

0.059

GERP RS

5.6

Varity_R

0.073

gMVP

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.

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