rs993598

Positions:

• chr2-178317968-G-A
• chr2-178317968-G-T

Variant summary

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

The NM_032523.4(OSBPL6):​c.103-6209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,990 control chromosomes in the GnomAD database, including 14,245 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 0.42 (14245 hom., cov: 32)
• Consequence: OSBPL6 NM_032523.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

Genes affected

OSBPL6 (HGNC:16388): (oxysterol binding protein like 6) 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. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL6	NM_032523.4	c.103-6209G>A		intron_variant		ENST00000190611.9	NP_115912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL6	ENST00000190611.9	c.103-6209G>A		intron_variant		1	NM_032523.4	ENSP00000190611	A1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63809 AN: 151870 Hom.: 14240 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.420 AC: 63834 AN: 151990 Hom.: 14245 Cov.: 32 AF XY: 0.421 AC XY: 31253 AN XY: 74270

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.452

Alfa AF: 0.469 Hom.: 23699

Bravo AF: 0.412

Asia WGS AF: 0.492 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.75

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: rs993598; hg19: chr2-179182695;