11-3092500-G-A

Position:

• chr11-3092500-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020896.4(OSBPL5):​c.2191C>T​(p.Arg731Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000771 in 1,427,310 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

ACMG classification

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=0.3401312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL5	NM_020896.4	c.2191C>T	p.Arg731Trp	missense_variant	19/22	ENST00000263650.12	NP_065947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12	c.2191C>T	p.Arg731Trp	missense_variant	19/22	1	NM_020896.4	ENSP00000263650	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000771 AC: 11 AN: 1427310 Hom.: 0 Cov.: 32 AF XY: 0.00000990 AC XY: 7 AN XY: 707036

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.0000755

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: 0.00000548

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000227

ExAC AF: 0.00000834 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.2191C>T (p.R731W) alteration is located in exon 19 (coding exon 18) of the OSBPL5 gene. This alteration results from a C to T substitution at nucleotide position 2191, causing the arginine (R) at amino acid position 731 to be replaced by a tryptophan (W). 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	0.090
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;.;T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D;.;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.
MutationTaster	Benign	0.88	N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;T;T;T;T;T
Polyphen		0.93	.;P;.;.;.;.
Vest4		0.24
MutPred		0.65		.;Loss of disorder (P = 0.0155);.;.;.;.;
MVP		0.50
MPC		0.27
ClinPred		0.66	D
GERP RS		2.6
Varity_R		0.079
gMVP		0.47

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

Other links and lift over

dbSNP: rs778874744; hg19: chr11-3113730;