rs75323599

Variant names:

• chr20-62256373-C-A
• rs75323599
• NM_144498.4:c.37+152C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144498.4(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 NM_144498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31
• Publications: 1 publications found

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]

OSBPL2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 67

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	NM_144498.4	MANE Select	c.37+152C>A		intron	N/A	NP_653081.1	Q9H1P3-1
	OSBPL2	NM_014835.5		c.37+152C>A		intron	N/A	NP_055650.1	Q9H1P3-2
	OSBPL2	NM_001363878.2		c.-330+152C>A		intron	N/A	NP_001350807.1	A0A2R8YDU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	ENST00000313733.9	TSL:1 MANE Select	c.37+152C>A		intron	N/A	ENSP00000316649.3	Q9H1P3-1
	OSBPL2	ENST00000358053.3	TSL:1	c.37+152C>A		intron	N/A	ENSP00000350755.2	Q9H1P3-2
	OSBPL2	ENST00000865094.1		c.37+152C>A		intron	N/A	ENSP00000535153.1

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

African (AFR) AF: 0.0232 AC: 259 AN: 11150

American (AMR) AF: 0.0376 AC: 451 AN: 12008

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 985 AN: 13438

East Asian (EAS) AF: 0.00 AC: 0 AN: 26358

South Asian (SAS) AF: 0.0604 AC: 2241 AN: 37080

European-Finnish (FIN) AF: 0.0960 AC: 3562 AN: 37098

Middle Eastern (MID) AF: 0.0822 AC: 167 AN: 2032

European-Non Finnish (NFE) AF: 0.0887 AC: 26056 AN: 293884

Other (OTH) AF: 0.0742 AC: 1872 AN: 25228

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

African (AFR) AF: 0.0243 AC: 1009 AN: 41560

American (AMR) AF: 0.0503 AC: 769 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1136 AN: 10602

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0937 AC: 6375 AN: 68016

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0778 Hom.: 159

Bravo AF: 0.0602

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.039
DANN	Benign	0.46
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75323599; hg19: chr20-60831429;