11-3089909-C-T

Variant names:

• chr11-3089909-C-T
• rs549339222
• NM_020896.4:c.2438G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020896.4(OSBPL5):​c.2438G>A​(p.Arg813Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,566,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R813W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.321
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010727137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL5	NM_020896.4	c.2438G>A	p.Arg813Gln	missense_variant	Exon 21 of 22	ENST00000263650.12	NP_065947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12	c.2438G>A	p.Arg813Gln	missense_variant	Exon 21 of 22	1	NM_020896.4	ENSP00000263650.7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000623 AC: 11 AN: 176456 AF XY: 0.0000526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000331

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 28 AN: 1414292 Hom.: 0 Cov.: 31 AF XY: 0.0000200 AC XY: 14 AN XY: 699436

African (AFR) AF: 0.00 AC: 0 AN: 32438

American (AMR) AF: 0.000209 AC: 8 AN: 38310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36990

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80290

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.0000129 AC: 14 AN: 1088314

Other (OTH) AF: 0.0000683 AC: 4 AN: 58588

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74424

African (AFR) AF: 0.00 AC: 0 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000509 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2438G>A (p.R813Q) alteration is located in exon 21 (coding exon 20) of the OSBPL5 gene. This alteration results from a G to A substitution at nucleotide position 2438, causing the arginine (R) at amino acid position 813 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	0.062
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.011	.;T;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.43	T;T;.;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.011	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	.;N;.;.;.;.
PhyloP100		0.32
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.80	N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.59	T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;T
Polyphen		0.0040	.;B;.;.;.;.
Vest4		0.096
MutPred		0.39		.;Loss of MoRF binding (P = 0.0255);.;.;.;.;
MVP		0.26
MPC		0.17
ClinPred		0.014	T
GERP RS		-2.3
Varity_R		0.029
gMVP		0.099
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs549339222; hg19: chr11-3111139;