chr11-3090677-C-T

Variant names:

• chr11-3090677-C-T
• rs377167443
• NM_020896.4:c.2279G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020896.4(OSBPL5):​c.2279G>A​(p.Arg760Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,611,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11652812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020896.4. 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
	OSBPL5	NM_020896.4	MANE Select	c.2279G>A	p.Arg760Gln	missense	Exon 20 of 22	NP_065947.1	Q9H0X9-1
	OSBPL5	NM_001144063.2		c.2075G>A	p.Arg692Gln	missense	Exon 19 of 21	NP_001137535.1	Q9H0X9-2
	OSBPL5	NM_145638.3		c.2075G>A	p.Arg692Gln	missense	Exon 19 of 21	NP_663613.1	Q9H0X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL5	ENST00000263650.12	TSL:1 MANE Select	c.2279G>A	p.Arg760Gln	missense	Exon 20 of 22	ENSP00000263650.7	Q9H0X9-1
	OSBPL5	ENST00000389989.7	TSL:1	c.2075G>A	p.Arg692Gln	missense	Exon 19 of 21	ENSP00000374639.3	Q9H0X9-2
	OSBPL5	ENST00000866647.1		c.2279G>A	p.Arg760Gln	missense	Exon 20 of 22	ENSP00000536706.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152266 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1459558 Hom.: 0 Cov.: 32 AF XY: 0.0000455 AC XY: 33 AN XY: 726060

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111648

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152266 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74388

African (AFR) AF: 0.0000482 AC: 2 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000680

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00000825 AC: 1

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	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.057
Sift	Uncertain	0.018	D
Sift4G	Benign	0.080	T
Polyphen		0.45	P
Vest4		0.16
MVP		0.45
MPC		0.19
ClinPred		0.096	T
GERP RS		2.9
Varity_R		0.039
gMVP		0.33
Mutation Taster		=86/14	polymorphism

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: rs377167443; hg19: chr11-3111907;