chr2-178332988-A-G

Variant names:

• chr2-178332988-A-G
• rs764056262
• NM_032523.4:c.604A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032523.4(OSBPL6):​c.604A>G​(p.Thr202Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. T202R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (1 hom.)
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03456089).

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.604A>G	p.Thr202Ala	missense	Exon 8 of 25	NP_115912.1	Q9BZF3-1
	OSBPL6	NM_001201480.2		c.604A>G	p.Thr202Ala	missense	Exon 8 of 26	NP_001188409.1	Q9BZF3-5
	OSBPL6	NM_145739.3		c.541A>G	p.Thr181Ala	missense	Exon 6 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.604A>G	p.Thr202Ala	missense	Exon 8 of 25	ENSP00000190611.4	Q9BZF3-1
	OSBPL6	ENST00000392505.6	TSL:1	c.604A>G	p.Thr202Ala	missense	Exon 8 of 26	ENSP00000376293.2	Q9BZF3-5
	OSBPL6	ENST00000409631.5	TSL:1	c.604A>G	p.Thr202Ala	missense	Exon 7 of 23	ENSP00000386885.1	Q9BZF3-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000995 AC: 25 AN: 251240 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461856 Hom.: 1 Cov.: 31 AF XY: 0.0000468 AC XY: 34 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.000131 AC: 2 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000824 AC: 10

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	Benign	0.055
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.10
Sift	Benign	0.30	T
Sift4G	Benign	0.51	T
Polyphen		0.0010	B
Vest4		0.088
MutPred		0.064		Loss of glycosylation at T202 (P = 0.0203)
MVP		0.10
MPC		0.29
ClinPred		0.034	T
GERP RS		5.6
Varity_R		0.089
gMVP		0.18
Mutation Taster		=81/19	polymorphism

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: rs764056262; hg19: chr2-179197715;