17-47809393-C-T

Position:

• chr17-47809393-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSBPL7	NM_145798.3	c.1966G>A	p.Glu656Lys	missense_variant	19/23	ENST00000007414.8
OSBPL7	XM_047435292.1	c.1966G>A	p.Glu656Lys	missense_variant	19/23
OSBPL7	XM_047435293.1	c.1912G>A	p.Glu638Lys	missense_variant	18/22
OSBPL7	XR_934362.2	n.2182G>A		non_coding_transcript_exon_variant	19/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBPL7	ENST00000007414.8	c.1966G>A	p.Glu656Lys	missense_variant	19/23	1	NM_145798.3	P1
OSBPL7	ENST00000613735.4	c.*246-278G>A		intron_variant, NMD_transcript_variant		1
OSBPL7	ENST00000583167.5	n.3016G>A		non_coding_transcript_exon_variant	7/11	2
OSBPL7	ENST00000579728.5	c.*781G>A		3_prime_UTR_variant, NMD_transcript_variant	18/22	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.1966G>A (p.E656K) alteration is located in exon 19 (coding exon 18) of the OSBPL7 gene. This alteration results from a G to A substitution at nucleotide position 1966, causing the glutamic acid (E) at amino acid position 656 to be replaced by a lysine (K). 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	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;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;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.62		Gain of MoRF binding (P = 0.0167);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

Publications

LitVar

Other links and lift over

dbSNP: rs2032964852; hg19: chr17-45886759;