rs747347987

Variant names:

• chr17-47813834-C-A
• NM_145798.3:c.1352G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-47813834-C-A
• chr17-47813834-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145798.3(OSBPL7):​c.1352G>T​(p.Gly451Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OSBPL7 NM_145798.3 missense, splice_region
• Scores: Splicing: ADA: 0.9018
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08500311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL7	NM_145798.3	c.1352G>T	p.Gly451Val	missense_variant, splice_region_variant	Exon 15 of 23	ENST00000007414.8	NP_665741.1
OSBPL7	XM_047435292.1	c.1352G>T	p.Gly451Val	missense_variant, splice_region_variant	Exon 15 of 23		XP_047291248.1
OSBPL7	XM_047435293.1	c.1298G>T	p.Gly433Val	missense_variant, splice_region_variant	Exon 14 of 22		XP_047291249.1
OSBPL7	XR_934362.2	n.1568G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 15 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8	c.1352G>T	p.Gly451Val	missense_variant, splice_region_variant	Exon 15 of 23	1	NM_145798.3	ENSP00000007414.3
OSBPL7	ENST00000613735.4	n.*245+1504G>T		intron_variant	Intron 12 of 15	1		ENSP00000479827.1
OSBPL7	ENST00000583167.5	n.2402G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 11	2
OSBPL7	ENST00000579728.5	n.*182-15G>T		intron_variant	Intron 13 of 21	5		ENSP00000463599.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452836 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 722500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.32
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.018
Sift	Benign	0.30	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.025	B;B
Vest4		0.30
MutPred		0.37		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.64
MPC		0.52
ClinPred		0.066	T
GERP RS		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.90
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-45891200;