rs3741350

Positions:

• chr11-3107797-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020896.4(OSBPL5):​c.840C>T​(p.Thr280Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,611,992 control chromosomes in the GnomAD database, including 162,251 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 0.50 (20749 hom., cov: 32)
  • Exomes 𝑓: 0.43 (141502 hom.)
• Consequence: OSBPL5 NM_020896.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

OSBPL5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL5	NM_020896.4	c.840C>T	p.Thr280Thr	synonymous_variant	8/22	ENST00000263650.12	NP_065947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12	c.840C>T	p.Thr280Thr	synonymous_variant	8/22	1	NM_020896.4	ENSP00000263650.7

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75399 AN: 151846 Hom.: 20707 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.475

GnomAD3 exomes AF: 0.409 AC: 101557 AN: 248518 Hom.: 23407 AF XY: 0.412 AC XY: 55489 AN XY: 134764

Gnomad AFR exome AF: 0.737

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.0394

Gnomad SAS exome AF: 0.485

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.432 AC: 630326 AN: 1460026 Hom.: 141502 Cov.: 66 AF XY: 0.432 AC XY: 313598 AN XY: 726366

Gnomad4 AFR exome AF: 0.734

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.0686

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.497 AC: 75501 AN: 151966 Hom.: 20749 Cov.: 32 AF XY: 0.490 AC XY: 36401 AN XY: 74250

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.473

Alfa AF: 0.458 Hom.: 11386

Bravo AF: 0.504

Asia WGS AF: 0.295 AC: 1025 AN: 3478

EpiCase AF: 0.440

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741350; hg19: chr11-3129027; COSMIC: COSV55139304;