17-47809190-C-G

Variant names:

• chr17-47809190-C-G
• rs758130888
• NM_145798.3:c.2056G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145798.3(OSBPL7):​c.2056G>C​(p.Val686Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.06

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL7	NM_145798.3	c.2056G>C	p.Val686Leu	missense_variant	Exon 20 of 23	ENST00000007414.8	NP_665741.1
OSBPL7	XM_047435292.1	c.2056G>C	p.Val686Leu	missense_variant	Exon 20 of 23		XP_047291248.1
OSBPL7	XM_047435293.1	c.2002G>C	p.Val668Leu	missense_variant	Exon 19 of 22		XP_047291249.1
OSBPL7	XR_934362.2	n.2272G>C		non_coding_transcript_exon_variant	Exon 20 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8	c.2056G>C	p.Val686Leu	missense_variant	Exon 20 of 23	1	NM_145798.3	ENSP00000007414.3
OSBPL7	ENST00000613735.4	n.*246-75G>C		intron_variant	Intron 12 of 15	1		ENSP00000479827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251220 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2056G>C (p.V686L) alteration is located in exon 20 (coding exon 19) of the OSBPL7 gene. This alteration results from a G to C substitution at nucleotide position 2056, causing the valine (V) at amino acid position 686 to be replaced by a leucine (L). 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	0.65
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.98	D;D
Vest4		0.68
MutPred		0.45		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.68
MPC		0.42
ClinPred		0.71	D
GERP RS		5.0
Varity_R		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs758130888; hg19: chr17-45886556;