rs2277301

Positions:

• chr11-3090636-C-A
• chr11-3090636-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020896.4(OSBPL5):​c.2320G>T​(p.Ala774Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A774T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 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=0.049062073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSBPL5	NM_020896.4	c.2320G>T	p.Ala774Ser	missense_variant	20/22	ENST00000263650.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBPL5	ENST00000263650.12	c.2320G>T	p.Ala774Ser	missense_variant	20/22	1	NM_020896.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.30
DEOGEN2	Benign	0.0036	.;T;.;T;.;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	T;T;.;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.049	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;N;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.080	N;N;N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.75	T;T;T;T;T;T
Sift4G	Benign	0.84	T;T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.;.
Vest4		0.10
MutPred		0.23		.;Gain of phosphorylation at A774 (P = 0.0022);.;.;.;.;
MVP		0.32
MPC		0.15
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.058
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3111866;