chr12-76481681-C-T

Variant names:

• chr12-76481681-C-T
• rs10506718
• NM_020841.5:c.42+5829G>A

Variant summary

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

The NM_020841.5(OSBPL8):​c.42+5829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,112 control chromosomes in the GnomAD database, including 3,408 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 0.20 (3408 hom., cov: 32)
• Consequence: OSBPL8 NM_020841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 3 publications found

Genes affected

OSBPL8 (HGNC:16396): (oxysterol binding protein like 8) This gene encodes a member of a family of proteins containing an N-terminal pleckstrin homology domain and a highly conserved C-terminal oxysterol-binding protein-like sterol-binding domain. It binds mutliple lipid-containing molecules, including phosphatidylserine, phosphatidylinositol 4-phosphate (PI4P) and oxysterol, and promotes their exchange between the endoplasmic reticulum and the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL8	NM_020841.5	c.42+5829G>A		intron_variant	Intron 2 of 23	ENST00000261183.8	NP_065892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL8	ENST00000261183.8	c.42+5829G>A		intron_variant	Intron 2 of 23	1	NM_020841.5	ENSP00000261183.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31030 AN: 151994 Hom.: 3410 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 31048 AN: 152112 Hom.: 3408 Cov.: 32 AF XY: 0.198 AC XY: 14697 AN XY: 74348

African (AFR) AF: 0.163 AC: 6779 AN: 41498

American (AMR) AF: 0.142 AC: 2171 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3470

East Asian (EAS) AF: 0.0763 AC: 395 AN: 5180

South Asian (SAS) AF: 0.127 AC: 610 AN: 4822

European-Finnish (FIN) AF: 0.194 AC: 2049 AN: 10560

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17842 AN: 67990

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.234 Hom.: 654

Bravo AF: 0.199

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		0.42
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: rs10506718; hg19: chr12-76875461;