20-62238609-C-T

Position:

• chr20-62238609-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144498.4(OSBPL2):​c.-129+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 148,048 control chromosomes in the GnomAD database, including 11,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11617 hom., cov: 29)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: OSBPL2 NM_144498.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.362

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 20-62238609-C-T is Benign according to our data. Variant chr20-62238609-C-T is described in ClinVar as [Benign]. Clinvar id is 1301807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.-129+12C>T		intron_variant		ENST00000313733.9	NP_653081.1
OSBPL2	NM_001278649.3	c.-350+12C>T		intron_variant			NP_001265578.1
OSBPL2	NM_001363878.2	c.-495+12C>T		intron_variant			NP_001350807.1
OSBPL2	NM_014835.5	c.-129+12C>T		intron_variant			NP_055650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.-129+12C>T		intron_variant		1	NM_144498.4	ENSP00000316649	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 55075 AN: 147910 Hom.: 11618 Cov.: 29

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.400 AC: 12 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.429

GnomAD4 genome AF: 0.372 AC: 55088 AN: 148018 Hom.: 11617 Cov.: 29 AF XY: 0.375 AC XY: 27035 AN XY: 72096

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.405

Alfa AF: 0.404 Hom.: 1653

Bravo AF: 0.368

Asia WGS AF: 0.490 AC: 1457 AN: 2970

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Feb 11, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

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: rs60622969; hg19: chr20-60813665;