rs1040002

Variant names:

• chr12-76554580-G-A
• rs1040002
• NM_020841.5:c.-68+4817C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-76554580-G-A
• chr12-76554580-G-C

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+4817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,974 control chromosomes in the GnomAD database, including 5,321 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 0.24 (5321 hom., cov: 32)
• Consequence: OSBPL8 NM_020841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.357 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+4817C>T		intron	N/A	NP_065892.1	Q9BZF1-1
	OSBPL8	NM_001319653.2		c.-68+4817C>T		intron	N/A	NP_001306582.1
	OSBPL8	NM_001003712.2		c.-148+4817C>T		intron	N/A	NP_001003712.1	Q9BZF1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL8	ENST00000261183.8	TSL:1 MANE Select	c.-68+4817C>T		intron	N/A	ENSP00000261183.3	Q9BZF1-1
	OSBPL8	ENST00000393249.6	TSL:1	c.-273+4817C>T		intron	N/A	ENSP00000376939.2	Q9BZF1-3
	OSBPL8	ENST00000611266.4	TSL:1	c.-194+4817C>T		intron	N/A	ENSP00000478240.1	Q9BZF1-3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36490 AN: 151856 Hom.: 5320 Cov.: 32

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.240 AC: 36497 AN: 151974 Hom.: 5321 Cov.: 32 AF XY: 0.241 AC XY: 17916 AN XY: 74282

African (AFR) AF: 0.0682 AC: 2830 AN: 41476

American (AMR) AF: 0.365 AC: 5569 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1048 AN: 3462

East Asian (EAS) AF: 0.349 AC: 1808 AN: 5174

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4822

European-Finnish (FIN) AF: 0.238 AC: 2511 AN: 10532

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20708 AN: 67918

Other (OTH) AF: 0.273 AC: 575 AN: 2108

Alfa AF: 0.294 Hom.: 13975

Bravo AF: 0.246

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		0.25
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: rs1040002; hg19: chr12-76948360;