2-178339705-C-T

Variant names:

• chr2-178339705-C-T
• rs150008222
• NM_032523.4:c.928C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032523.4(OSBPL6):​c.928C>T​(p.Arg310Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,603,520 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R310Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.86
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14945829).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032523.4. 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
	OSBPL6	NM_032523.4	MANE Select	c.928C>T	p.Arg310Trp	missense	Exon 11 of 25	NP_115912.1	Q9BZF3-1
	OSBPL6	NM_001201480.2		c.928C>T	p.Arg310Trp	missense	Exon 11 of 26	NP_001188409.1	Q9BZF3-5
	OSBPL6	NM_145739.3		c.865C>T	p.Arg289Trp	missense	Exon 9 of 24	NP_665682.1	Q9BZF3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL6	ENST00000190611.9	TSL:1 MANE Select	c.928C>T	p.Arg310Trp	missense	Exon 11 of 25	ENSP00000190611.4	Q9BZF3-1
	OSBPL6	ENST00000392505.6	TSL:1	c.928C>T	p.Arg310Trp	missense	Exon 11 of 26	ENSP00000376293.2	Q9BZF3-5
	OSBPL6	ENST00000409631.5	TSL:1	c.928C>T	p.Arg310Trp	missense	Exon 10 of 23	ENSP00000386885.1	Q9BZF3-2

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151582 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000194 AC: 47 AN: 242884 AF XY: 0.000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000496

Gnomad ASJ exome AF: 0.000402

Gnomad EAS exome AF: 0.0000566

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000216

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000145 AC: 210 AN: 1451820 Hom.: 1 Cov.: 30 AF XY: 0.000133 AC XY: 96 AN XY: 722174

African (AFR) AF: 0.00 AC: 0 AN: 32938

American (AMR) AF: 0.000464 AC: 20 AN: 43138

Ashkenazi Jewish (ASJ) AF: 0.000424 AC: 11 AN: 25950

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 84448

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1107500

Other (OTH) AF: 0.000250 AC: 15 AN: 59976

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151700 Hom.: 0 Cov.: 33 AF XY: 0.000216 AC XY: 16 AN XY: 74168

African (AFR) AF: 0.0000242 AC: 1 AN: 41332

American (AMR) AF: 0.000394 AC: 6 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 3 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000310 AC: 21 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.000211 Hom.: 0

Bravo AF: 0.000219

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000214 AC: 26

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.61
MVP		0.19
MPC		0.73
ClinPred		0.46	T
GERP RS		3.9
Varity_R		0.76
gMVP		0.58
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150008222; hg19: chr2-179204432; COSMIC: COSV51925382;