Variant 18-24165104-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080597.4(OSBPL1A):c.2711G>A(p.Arg904His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,962 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OSBPL1A
NM_080597.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

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 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, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL1A	NM_080597.4 linkuse as main transcript	c.2711G>A	p.Arg904His	missense_variant	27/28	ENST00000319481.8	NP_542164.2	Q9BXW6-1B0YJ56B3KU11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OSBPL1A	ENST00000319481.8 linkuse as main transcript	c.2711G>A	p.Arg904His	missense_variant	27/28	1	NM_080597.4	ENSP00000320291.3	Q9BXW6-1
OSBPL1A	ENST00000399443.7 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	13/14	1		ENSP00000382372.3	Q9BXW6-2
OSBPL1A	ENST00000357041.8 linkuse as main transcript	c.1565G>A	p.Arg522His	missense_variant	15/16	2		ENSP00000349545.4	Q9BXW6-4
OSBPL1A	ENST00000578013.1 linkuse as main transcript	c.716G>A	p.Arg239His	missense_variant	7/8	5		ENSP00000464617.1	J3QSB8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251468

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

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

Jun 23, 2023

The c.2711G>A (p.R904H) alteration is located in exon 27 (coding exon 26) of the OSBPL1A gene. This alteration results from a G to A substitution at nucleotide position 2711, causing the arginine (R) at amino acid position 904 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

Pathogenic

0.67

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.;.;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.065

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Uncertain

0.011

MutationAssessor

Pathogenic

4.0

H;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

D;D;D;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.76

MVP

0.68

MPC

1.9

ClinPred

1.0

GERP RS

5.8

Varity_R

0.86

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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