17-47813660-C-A

Variant names:

• chr17-47813660-C-A
• rs749751186
• NM_145798.3:c.1526G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145798.3(OSBPL7):​c.1526G>T​(p.Arg509Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R509Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 publications found

Genes affected

OSBPL7 (HGNC:16387): (oxysterol binding protein like 7) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Two transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145798.3. 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
	OSBPL7	NM_145798.3	MANE Select	c.1526G>T	p.Arg509Leu	missense	Exon 15 of 23	NP_665741.1	Q9BZF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL7	ENST00000007414.8	TSL:1 MANE Select	c.1526G>T	p.Arg509Leu	missense	Exon 15 of 23	ENSP00000007414.3	Q9BZF2-1
	OSBPL7	ENST00000613735.4	TSL:1	n.*245+1678G>T		intron	N/A	ENSP00000479827.1	Q9BZF2-2
	OSBPL7	ENST00000915866.1		c.1526G>T	p.Arg509Leu	missense	Exon 15 of 23	ENSP00000585925.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.73		Loss of helix (P = 0.0626)
MVP		0.64
MPC		1.4
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs749751186; hg19: chr17-45891026;