17-47815247-C-T

Variant names:

• chr17-47815247-C-T
• rs142011621
• NM_145798.3:c.1225G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145798.3(OSBPL7):​c.1225G>A​(p.Val409Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32398513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL7	NM_145798.3	c.1225G>A	p.Val409Ile	missense_variant	Exon 13 of 23	ENST00000007414.8	NP_665741.1
OSBPL7	XM_047435292.1	c.1225G>A	p.Val409Ile	missense_variant	Exon 13 of 23		XP_047291248.1
OSBPL7	XM_047435293.1	c.1171G>A	p.Val391Ile	missense_variant	Exon 12 of 22		XP_047291249.1
OSBPL7	XR_934362.2	n.1441G>A		non_coding_transcript_exon_variant	Exon 13 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8	c.1225G>A	p.Val409Ile	missense_variant	Exon 13 of 23	1	NM_145798.3	ENSP00000007414.3
OSBPL7	ENST00000613735.4	n.*245+91G>A		intron_variant	Intron 12 of 15	1		ENSP00000479827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250598 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135530

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

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 AF: 0.00000137 AC: 2 AN: 1461536 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.53
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.98	D;D
Vest4		0.47
MutPred		0.32		Loss of catalytic residue at V409 (P = 0.0291);Loss of catalytic residue at V409 (P = 0.0291);
MVP		0.58
MPC		1.1
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.29

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: rs142011621; hg19: chr17-45892613;