11-3090636-C-T

Variant names:

• chr11-3090636-C-T
• rs2277301
• NM_020896.4:c.2320G>A
• OSBPL5 p.Ala774Thr

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020896.4(OSBPL5):​c.2320G>A​(p.Ala774Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,612,596 control chromosomes in the GnomAD database, including 34,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3158 hom., cov: 34)
  • Exomes 𝑓: 0.20 (31273 hom.)
• Consequence: OSBPL5 NM_020896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033494234).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

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.2320G>A	p.Ala774Thr	missense	Exon 20 of 22	NP_065947.1	Q9H0X9-1
	OSBPL5	NM_001144063.2		c.2116G>A	p.Ala706Thr	missense	Exon 19 of 21	NP_001137535.1	Q9H0X9-2
	OSBPL5	NM_145638.3		c.2116G>A	p.Ala706Thr	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.2320G>A	p.Ala774Thr	missense	Exon 20 of 22	ENSP00000263650.7	Q9H0X9-1
	OSBPL5	ENST00000389989.7	TSL:1	c.2116G>A	p.Ala706Thr	missense	Exon 19 of 21	ENSP00000374639.3	Q9H0X9-2
	OSBPL5	ENST00000866647.1		c.2320G>A	p.Ala774Thr	missense	Exon 20 of 22	ENSP00000536706.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29252 AN: 152152 Hom.: 3157 Cov.: 34

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.194 AC: 48302 AN: 248928 AF XY: 0.203

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0902

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.0279

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.200 AC: 291829 AN: 1460324 Hom.: 31273 Cov.: 34 AF XY: 0.203 AC XY: 147227 AN XY: 726460

African (AFR) AF: 0.157 AC: 5239 AN: 33474

American (AMR) AF: 0.0951 AC: 4248 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4781 AN: 26108

East Asian (EAS) AF: 0.0611 AC: 2425 AN: 39686

South Asian (SAS) AF: 0.278 AC: 23950 AN: 86228

European-Finnish (FIN) AF: 0.358 AC: 18701 AN: 52284

Middle Eastern (MID) AF: 0.176 AC: 1015 AN: 5762

European-Non Finnish (NFE) AF: 0.198 AC: 220090 AN: 1111748

Other (OTH) AF: 0.189 AC: 11380 AN: 60342

GnomAD4 genome AF: 0.192 AC: 29267 AN: 152272 Hom.: 3158 Cov.: 34 AF XY: 0.199 AC XY: 14817 AN XY: 74438

African (AFR) AF: 0.160 AC: 6651 AN: 41572

American (AMR) AF: 0.140 AC: 2141 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3472

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5174

South Asian (SAS) AF: 0.267 AC: 1288 AN: 4832

European-Finnish (FIN) AF: 0.372 AC: 3947 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13776 AN: 68004

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.189 Hom.: 1821

Bravo AF: 0.166

Asia WGS AF: 0.159 AC: 550 AN: 3478

EpiCase AF: 0.195

EpiControl AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.70
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		2.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.066
Sift	Benign	0.59	T
Sift4G	Benign	1.0	T
Varity_R		0.055
gMVP		0.19
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2277301;

hg19: chr11-3111866;

COSMIC: COSV55139085;

COSMIC: COSV55139085;