OSBPL5 p.Ala774Ser

Variant names:

• chr11-3090636-C-A
• rs2277301
• NM_020896.4:c.2320G>T
• OSBPL5 p.Ala774Ser

Your query was ambiguous. Multiple possible variants found:

• chr11-3090636-C-A
• chr11-3090634-GGC-AGA
• chr11-3090634-GGC-TGA
• chr11-3090634-GGC-CGA
• chr11-3090635-GC-CT
• chr11-3090634-GGC-ACT

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049062073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL5	NM_020896.4	MANE Select	c.2320G>T	p.Ala774Ser	missense	Exon 20 of 22	NP_065947.1	Q9H0X9-1
	OSBPL5	NM_001144063.2		c.2116G>T	p.Ala706Ser	missense	Exon 19 of 21	NP_001137535.1	Q9H0X9-2
	OSBPL5	NM_145638.3		c.2116G>T	p.Ala706Ser	missense	Exon 19 of 21	NP_663613.1	Q9H0X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL5	ENST00000263650.12	TSL:1 MANE Select	c.2320G>T	p.Ala774Ser	missense	Exon 20 of 22	ENSP00000263650.7	Q9H0X9-1
	OSBPL5	ENST00000389989.7	TSL:1	c.2116G>T	p.Ala706Ser	missense	Exon 19 of 21	ENSP00000374639.3	Q9H0X9-2
	OSBPL5	ENST00000866647.1		c.2320G>T	p.Ala774Ser	missense	Exon 20 of 22	ENSP00000536706.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.052
Sift	Benign	0.75	T
Sift4G	Benign	0.84	T
Varity_R		0.058
gMVP		0.22
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2277301;

hg19: chr11-3111866;