chr20-62286726-A-G

Position:

• chr20-62286726-A-G

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.1125+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,602,472 control chromosomes in the GnomAD database, including 166,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14774 hom., cov: 33)
  • Exomes 𝑓: 0.46 (151457 hom.)
• Consequence: OSBPL2 NM_144498.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.80

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=-0.99).
• BP6: Variant 20-62286726-A-G is Benign according to our data. Variant chr20-62286726-A-G is described in ClinVar as [Benign]. Clinvar id is 517559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.1125+15A>G		intron_variant		ENST00000313733.9	NP_653081.1
OSBPL2	NM_014835.5	c.1089+15A>G		intron_variant			NP_055650.1
OSBPL2	NM_001363878.2	c.849+15A>G		intron_variant			NP_001350807.1
OSBPL2	NM_001278649.3	c.849+15A>G		intron_variant			NP_001265578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.1125+15A>G		intron_variant		1	NM_144498.4	ENSP00000316649.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66872 AN: 152026 Hom.: 14769 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.454

GnomAD3 exomes AF: 0.433 AC: 107676 AN: 248534 Hom.: 23566 AF XY: 0.434 AC XY: 58319 AN XY: 134508

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.472

Gnomad SAS exome AF: 0.384

Gnomad FIN exome AF: 0.400

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.455 AC: 660439 AN: 1450328 Hom.: 151457 Cov.: 37 AF XY: 0.454 AC XY: 326456 AN XY: 719422

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.440 AC: 66922 AN: 152144 Hom.: 14774 Cov.: 33 AF XY: 0.433 AC XY: 32229 AN XY: 74366

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.450

Alfa AF: 0.456 Hom.: 3462

Bravo AF: 0.442

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

c.1125+15A>G in intron 11 of OSBPL2: This variant is not expected to have clinic al significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 47.57% (4077/85 70) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs2297592). -

Autosomal dominant nonsyndromic hearing loss 67 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.93
DANN	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2297592; hg19: chr20-60861782; COSMIC: COSV58215664; COSMIC: COSV58215664;