12-76405861-C-G

Position:

• chr12-76405861-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020841.5(OSBPL8):​c.289-3095G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,086 control chromosomes in the GnomAD database, including 45,575 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 0.77 (45575 hom., cov: 31)
• Consequence: OSBPL8 NM_020841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL8	NM_020841.5	c.289-3095G>C		intron_variant		ENST00000261183.8	NP_065892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL8	ENST00000261183.8	c.289-3095G>C		intron_variant		1	NM_020841.5	ENSP00000261183.3

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116479 AN: 151968 Hom.: 45522 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.767 AC: 116589 AN: 152086 Hom.: 45575 Cov.: 31 AF XY: 0.765 AC XY: 56888 AN XY: 74350

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.735

Alfa AF: 0.656 Hom.: 1908

Bravo AF: 0.761

Asia WGS AF: 0.759 AC: 2639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.46

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: rs2037581; hg19: chr12-76799641; COSMIC: COSV53888960;