12-76535195-T-A

Variant names:

• chr12-76535195-T-A
• rs10862080
• NM_020841.5:c.-68+24202A>T

Variant summary

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

The NM_020841.5(OSBPL8):​c.-68+24202A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,046 control chromosomes in the GnomAD database, including 1,278 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 0.11 (1278 hom., cov: 32)
• Consequence: OSBPL8 NM_020841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020841.5. 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
	OSBPL8	NM_020841.5	MANE Select	c.-68+24202A>T		intron	N/A	NP_065892.1
	OSBPL8	NM_001319653.2		c.-68+24202A>T		intron	N/A	NP_001306582.1
	OSBPL8	NM_001003712.2		c.-148+24202A>T		intron	N/A	NP_001003712.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL8	ENST00000261183.8	TSL:1 MANE Select	c.-68+24202A>T		intron	N/A	ENSP00000261183.3
	OSBPL8	ENST00000393249.6	TSL:1	c.-204-914A>T		intron	N/A	ENSP00000376939.2
	OSBPL8	ENST00000611266.4	TSL:1	c.-194+24202A>T		intron	N/A	ENSP00000478240.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16186 AN: 151928 Hom.: 1274 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.107 AC: 16198 AN: 152046 Hom.: 1278 Cov.: 32 AF XY: 0.114 AC XY: 8451 AN XY: 74358

African (AFR) AF: 0.0231 AC: 959 AN: 41522

American (AMR) AF: 0.121 AC: 1840 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1876 AN: 5182

South Asian (SAS) AF: 0.199 AC: 957 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1909 AN: 10512

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7779 AN: 67964

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.109 Hom.: 124

Bravo AF: 0.0959

Asia WGS AF: 0.275 AC: 946 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.67
DANN	Benign	0.25
PhyloP100		-0.52
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: rs10862080; hg19: chr12-76928975;