17-47816148-C-T

Position:

• chr17-47816148-C-T

Variant summary

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

The NM_145798.3(OSBPL7):​c.1078G>A​(p.Asp360Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000572 in 1,398,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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=0.33840626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL7	NM_145798.3	c.1078G>A	p.Asp360Asn	missense_variant	12/23	ENST00000007414.8	NP_665741.1
OSBPL7	XM_047435292.1	c.1078G>A	p.Asp360Asn	missense_variant	12/23		XP_047291248.1
OSBPL7	XM_047435293.1	c.1024G>A	p.Asp342Asn	missense_variant	11/22		XP_047291249.1
OSBPL7	XR_934362.2	n.1294G>A		non_coding_transcript_exon_variant	12/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8	c.1078G>A	p.Asp360Asn	missense_variant	12/23	1	NM_145798.3	ENSP00000007414.3
OSBPL7	ENST00000613735.4	n.*189G>A		non_coding_transcript_exon_variant	11/16	1		ENSP00000479827.1
OSBPL7	ENST00000613735.4	n.*189G>A		3_prime_UTR_variant	11/16	1		ENSP00000479827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000572 AC: 8 AN: 1398918 Hom.: 0 Cov.: 31 AF XY: 0.00000725 AC XY: 5 AN XY: 690000

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Cavalleri Lab, Royal College of Surgeons in Ireland

Mar 16, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.21
Sift	Benign	0.077	T;T
Sift4G	Benign	0.19	T;T
Polyphen		1.0	D;D
Vest4		0.29
MutPred		0.19		Gain of MoRF binding (P = 0.0413);Gain of MoRF binding (P = 0.0413);
MVP		0.67
MPC		0.79
ClinPred		0.78	D
GERP RS		4.5
Varity_R		0.097

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: rs1016471339; hg19: chr17-45893514;