chr20-62259975-G-A

Position:

• chr20-62259975-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000313733.9(OSBPL2):​c.38-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,611,242 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (34 hom.)
• Consequence: OSBPL2 ENST00000313733.9 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001437
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00600

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=-0.86).
• BP6: Variant 20-62259975-G-A is Benign according to our data. Variant chr20-62259975-G-A is described in ClinVar as [Benign]. Clinvar id is 508599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00201 (306/152158) while in subpopulation SAS AF= 0.0198 (95/4808). AF 95% confidence interval is 0.0165. There are 3 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.38-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000313733.9	NP_653081.1
OSBPL2	NM_001278649.3	c.-184-3641G>A		intron_variant			NP_001265578.1
OSBPL2	NM_001363878.2	c.-329-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001350807.1
OSBPL2	NM_014835.5	c.38-42G>A		intron_variant			NP_055650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.38-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_144498.4	ENSP00000316649	P1

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152040 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00204

Gnomad OTH AF: 0.00432

GnomAD3 exomes AF: 0.00379 AC: 943 AN: 249022 Hom.: 9 AF XY: 0.00475 AC XY: 639 AN XY: 134548

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00902

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0169

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00237

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00235 AC: 3425 AN: 1459084 Hom.: 34 Cov.: 30 AF XY: 0.00293 AC XY: 2129 AN XY: 725772

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00872

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0174

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152158 Hom.: 3 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74372

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0198

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.00204

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00256 Hom.: 1

Bravo AF: 0.00175

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00374

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Dec 25, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 02, 2018	- -
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	-0.86
CADD	Benign	0.81
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0020
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: rs186638612; hg19: chr20-60835031;