20-62256373-C-A

Position:

• chr20-62256373-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000313733.9(OSBPL2):​c.37+152C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 610,550 control chromosomes in the GnomAD database, including 2,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (413 hom., cov: 33)
  • Exomes 𝑓: 0.078 (1816 hom.)
• Consequence: OSBPL2 ENST00000313733.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31

Genes affected

OSBPL2 (HGNC:15761): (oxysterol binding protein like 2) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although the encoded protein contains only the sterol-binding domain. In vitro studies have shown that the encoded protein can bind strongly to phosphatic acid and weakly to phosphatidylinositol 3-phosphate, but cannot bind to 25-hydroxycholesterol. The protein associates with the Golgi apparatus. Transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-62256373-C-A is Benign according to our data. Variant chr20-62256373-C-A is described in ClinVar as [Benign]. Clinvar id is 1296854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.37+152C>A		intron_variant		ENST00000313733.9	NP_653081.1
OSBPL2	NM_001278649.3	c.-185+152C>A		intron_variant			NP_001265578.1
OSBPL2	NM_001363878.2	c.-330+152C>A		intron_variant			NP_001350807.1
OSBPL2	NM_014835.5	c.37+152C>A		intron_variant			NP_055650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.37+152C>A		intron_variant		1	NM_144498.4	ENSP00000316649	P1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10053 AN: 152156 Hom.: 413 Cov.: 33

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0650

GnomAD4 exome AF: 0.0777 AC: 35593 AN: 458276 Hom.: 1816 AF XY: 0.0769 AC XY: 18410 AN XY: 239546

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.0376

Gnomad4 ASJ exome AF: 0.0733

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0604

Gnomad4 FIN exome AF: 0.0960

Gnomad4 NFE exome AF: 0.0887

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0660 AC: 10049 AN: 152274 Hom.: 413 Cov.: 33 AF XY: 0.0651 AC XY: 4846 AN XY: 74456

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0566

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0805 Hom.: 92

Bravo AF: 0.0602

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.039
DANN	Benign	0.46

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: rs75323599; hg19: chr20-60831429;