rs2032964852

Variant names:

• chr17-47809393-C-T
• rs2032964852
• NM_145798.3:c.1966G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145798.3(OSBPL7):​c.1966G>A​(p.Glu656Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. E656D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

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.1966G>A	p.Glu656Lys	missense	Exon 19 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.1966G>A	p.Glu656Lys	missense	Exon 19 of 23	ENSP00000007414.3	Q9BZF2-1
	OSBPL7	ENST00000613735.4	TSL:1	n.*246-278G>A		intron	N/A	ENSP00000479827.1	Q9BZF2-2
	OSBPL7	ENST00000915866.1		c.1966G>A	p.Glu656Lys	missense	Exon 19 of 23	ENSP00000585925.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.62		Gain of MoRF binding (P = 0.0167)
MVP		0.86
MPC		1.3
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.75

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

Other links and lift over

dbSNP: rs2032964852; hg19: chr17-45886759;