20-62232970-C-T

Variant names:

• chr20-62232970-C-T
• rs6089695
• ENST00000615516.1:n.1049C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615516.1(OSBPL2):​n.1049C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 456,016 control chromosomes in the GnomAD database, including 42,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (12045 hom., cov: 32)
  • Exomes 𝑓: 0.45 (30893 hom.)
• Consequence: OSBPL2 ENST00000615516.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 16 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nonsyndromic genetic hearing loss

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105369209 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615516.1. 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
	LOC105369209	NR_160555.1		n.625C>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	ENST00000615516.1	TSL:2	n.1049C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56926 AN: 151888 Hom.: 12050 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.451 AC: 61090 AN: 135510 AF XY: 0.450

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.506

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.446 AC: 135557 AN: 304010 Hom.: 30893 Cov.: 0 AF XY: 0.447 AC XY: 77426 AN XY: 173102

African (AFR) AF: 0.149 AC: 1283 AN: 8628

American (AMR) AF: 0.510 AC: 13883 AN: 27226

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 4792 AN: 10758

East Asian (EAS) AF: 0.512 AC: 4712 AN: 9210

South Asian (SAS) AF: 0.441 AC: 26347 AN: 59682

European-Finnish (FIN) AF: 0.422 AC: 5385 AN: 12746

Middle Eastern (MID) AF: 0.440 AC: 1215 AN: 2760

European-Non Finnish (NFE) AF: 0.452 AC: 71695 AN: 158792

Other (OTH) AF: 0.440 AC: 6245 AN: 14208

GnomAD4 genome AF: 0.375 AC: 56937 AN: 152006 Hom.: 12045 Cov.: 32 AF XY: 0.378 AC XY: 28049 AN XY: 74278

African (AFR) AF: 0.148 AC: 6151 AN: 41480

American (AMR) AF: 0.463 AC: 7073 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2682 AN: 5150

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4820

European-Finnish (FIN) AF: 0.421 AC: 4460 AN: 10582

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31336 AN: 67904

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.443 Hom.: 26510

Bravo AF: 0.369

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6089695; hg19: chr20-60808026; COSMIC: COSV50778465;